Advertisement
British Journal of Anaesthesia
BJA

Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review

Open ArchivePublished:June 19, 2018DOI:https://doi.org/10.1016/j.bja.2018.04.036

      Abstract

      Background

      Intraoperative hypotension is a common side effect of general anaesthesia and might lead to inadequate organ perfusion. It is unclear to what extent hypotension during noncardiac surgery is associated with unfavourable outcomes.

      Methods

      We conducted a systematic search in PubMed, Embase, Web of Science, and CINAHL, and classified the quality of retrieved articles according to predefined adapted STROBE and CONSORT criteria. Reported strengths of associations from high-quality studies were classified into end-organ specific injury risks, such as acute kidney injury, myocardial injury, and stroke, and overall organ injury risks for various arterial blood pressure thresholds.

      Results

      We present an overview of 42 articles on reported associations between various absolute and relative intraoperative hypotension definitions and their associations with postoperative adverse outcomes after noncardiac surgery. Elevated risks of end-organ injury were reported for prolonged exposure (≥10 min) to mean arterial pressures <80 mm Hg and for shorter durations <70 mm Hg. Reported risks increase with increased durations for mean arterial pressures <65–60 mm Hg or for any exposure <55–50 mm Hg.

      Conclusions

      The reported associations suggest that organ injury might occur when mean arterial pressure decreases <80 mm Hg for ≥10 min, and that this risk increases with blood pressures becoming progressively lower. Given the retrospective observational design of the studies reviewed, reflected by large variability in patient characteristics, hypotension definitions and outcomes, solid conclusions on which blood pressures under which circumstances are truly too low cannot be drawn. We provide recommendations for the design of future studies.

      Clinical registration number

      (PROSPERO ID). CRD42013005171.

      Keywords

      • In a systematic review of the association between intraoperative hypotension and adverse postoperative outcomes in noncardiac surgery, 42 relevant studies were identified and analysed.
      • Elevated risks of end-organ injury were reported for exposures to mean arterial pressures <80 mm Hg for >10 min, and for shorter durations <70 mm Hg.
      • Elevated risks were reported for increased durations for mean arterial pressures <65–60 mm Hg or for any exposure <55–50 mm Hg.
      • Future prospective studies are indicated with less variability in patient characteristics and better definitions of hypotension and adverse outcomes.
      Intraoperative hypotension is a common side-effect of general anaesthesia that has received much attention in recent years because of its frequent occurrence and presumed adverse consequences. However, no widely accepted definition of intraoperative hypotension is available.
      • Bijker J.B.
      • van Klei W.A.
      • Kappen T.H.
      • van Wolfswinkel L.
      • Moons K.G.M.
      • Kalkman C.J.
      Incidence of intraoperative hypotension as a function of the chosen definition: literature definitions applied to a retrospective cohort using automated data collection.
      Despite this lack of a uniform definition, researchers have addressed the association between intraoperative hypotension and postoperative mortality and organ dysfunction after general anaesthesia. Monk and colleagues
      • Monk T.G.
      • Saini V.
      • Weldon B.C.
      • Sigl J.C.
      Anesthetic management and one-year mortality after noncardiac surgery.
      were one of the first groups to show a significant association between duration of intraoperative hypotension and mortality. More recent landmark studies have shown associations between hypotension and other adverse outcomes such as acute kidney injury (AKI) and myocardial injury (MI).
      • Sun L.Y.
      • Wijeysundera D.N.
      • Tait G.A.
      • Beattie W.S.
      Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery.
      • Walsh M.
      • Devereaux P.J.
      • Garg A.X.
      • et al.
      Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension.
      It remains a topic of debate if, and to what extent, hypotension disrupts organ perfusion resulting in organ damage. Furthermore, such organ damage might depend on the degree and duration of the hypotensive episodes. A summary of what is known about the effects of intraoperative hypotension on postoperative organ dysfunction and mortality is essential for anaesthesiologists to determine the range of blood pressures acceptable during surgery. So far, no systematic search of the literature has been conducted to summarise the available evidence regarding the association between intraoperative hypotension and adverse postoperative outcomes. As hypotension has not clearly been defined, such a summary needs to include an analysis of which blood pressure threshold an association with adverse outcomes becomes clinically relevant.
      We studied the relationship between intraoperative hypotension and postoperative adverse outcomes after noncardiac surgery by performing a systematic search of the literature. We classified studies according to quality criteria and report strengths of associations for various blood pressure thresholds and postoperative adverse outcomes.

      Methods

       Search strategy and selection of articles

      We conducted a systematic search of literature in PubMed, Embase, Web of Science, and CINAHL on March 8, 2017. Synonyms and medical subject headings for intraoperative hypotension were combined with synonyms and medical subject headings for complication, mortality, AKI, MI, ischaemic stroke, delirium, and length of hospital stay (LOS) as described in Box 1. The search filters were restricted to presence of the synonyms in titles and abstracts. No other limits were used. The articles obtained by this search were independently screened by two reviewers (E.W. and H.M.T.). In case of inconsistency, consensus was achieved by a third independent reviewer (T.H.K.). The reference lists of all selected and included articles were checked to retrieve relevant publications that were not found by the above described search strategy. The inclusion and exclusion criteria for publication type, study design, hypotension, and studied outcome definitions are described in Box 2.
      Search string
      Determinant: ((((hypotension[title and abstract] OR hypotensive[title and abstract]) AND (intraoperative[title and abstract] OR perioperative[title and abstract] OR intraoperatively[title and abstract] OR perioperatively[title and abstract] OR peroperative[title and abstract] OR peroperatively[title and abstract])))).
      Outcome: (mortal*[title and abstract] OR death[title and abstract] OR “moribund”[title and abstract] OR die*[title and abstract] OR fatal[title and abstract]) OR ((kidney[title and abstract] OR renal[title and abstract]) AND (insuff*[title and abstract] OR failure[title and abstract] OR injury[title and abstract] OR “ATN”[title and abstract]) OR (((heart[title and abstract] OR myocard*[title and abstract] OR cardial[title and abstract] OR coronary[title and abstract]) AND (ischem*[title and abstract] OR ischaem*[title and abstract] OR infarct*[title and abstract]) OR (acute AND coronary AND syndrome[title and abstract] OR ACS[title and abstract])) OR (((Brain[title and abstract] OR cerebr*[title and abstract]) AND (Vascular[title and abstract] OR cerebrovascular[title and abstract]) AND (embol*[title and abstract] OR accident*[title and abstract] OR complication*[title and abstract] OR ischaem*[title and abstract] OR ischem*[title and abstract] OR infarct*[title and abstract] OR incident*[title and abstract] OR stroke[title and abstract] OR stroke*[title and abstract] OR apoplexy[title and abstract]) OR (((Delirium[title and abstract] OR Deliriou*[title and abstract])) OR ((admission[title and abstract] OR stay[title and abstract]) AND (day*[title and abstract] OR duration[title and abstract] OR LOS[title and abstract] OR length[title and abstract]) OR (morbidity[title and abstract] OR complication[title and abstract] OR “adverse event”[title and abstract] OR “adverse events”[title and abstract]))
      Selection criteria
      Publication type
      • Full reports published before 8 March 2017.
      • Written in English or Dutch.
      Study design
      • Studies in which ≥50% of the adult patients underwent general anaesthesia or general anaesthesia combined with local or regional anaesthesia for noncardiac surgery were included. Studies in animals or children and emergency procedures for ruptured vessels were excluded.
      • Studies were excluded when they selected a subgroup of patients with a specific comorbidity that was not part of the reason to perform the surgical procedure.
      • The study design had to be a randomised controlled clinical trial, a cohort study or a case–control study with >10 patients. Case series, case reports, meta-analyses and (systematic) reviews were excluded.
      • The association between intraoperative hypotension and at least one outcome (mortality, acute kidney injury, myocardial injury, stroke, delirium, length of stay) had to be reported. The definition of determinant or outcome did not belong to the inclusion or exclusion criteria. Studies focusing on intentional or induced intraoperative hypotension or on the effects of antihypertensive medication were excluded.
      Definition of intraoperative hypotension
      • Intraoperative hypotension had to be defined in the article as an absolute or relative blood pressure threshold. Blood pressure thresholds had to be clinically relevant (i.e. not a mean blood pressure <100 mm Hg or >5% decrease compared with baseline blood pressure).

       Data extraction and quality assessment

      Data on study design, hypotension definitions, studied outcomes, and (adjusted) strengths of association were extracted from all included studies (Table 1, Table 2).
      • Monk T.G.
      • Saini V.
      • Weldon B.C.
      • Sigl J.C.
      Anesthetic management and one-year mortality after noncardiac surgery.
      • Sun L.Y.
      • Wijeysundera D.N.
      • Tait G.A.
      • Beattie W.S.
      Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery.
      • Walsh M.
      • Devereaux P.J.
      • Garg A.X.
      • et al.
      Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension.
      • Hirsch J.
      • DePalma G.
      • Tsai T.T.
      • Sands L.P.
      • Leung J.M.
      Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery.
      • Monk T.G.
      • Bronsert M.R.
      • Henderson W.G.
      • et al.
      Association between intraoperative hypotension and hypertension and 30-day postoperative mortality in noncardiac surgery.
      • Willingham M.D.
      • Karren E.
      • Shanks A.M.
      • et al.
      Concurrence of intraoperative hypotension, low minimum alveolar concentration, and low bispectral index is associated with postoperative death.
      • Bijker J.B.
      • Persoon S.
      • Peelen L.
      • et al.
      Intraoperative hypotension and perioperative ischemic stroke after general surgery.
      • Mizota T.
      • Hamada M.
      • Segawa H.
      Relationship between intraoperative hypotension and acute kidney injury after living donor liver transplantation: a retrospective analysis.
      • Schmid S.
      • Kapfer B.
      • Heim M.
      • et al.
      Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial.
      • Roshanov P.S.
      • Rochwerg B.
      • Patel A.
      • et al.
      Enzyme inhibitors or angiotensin II receptor blockers.
      • Salmasi V.
      • Maheshwari K.
      • Dongsheng Y.
      • et al.
      Thresholds, and acute kidney and myocardial injury after noncardiac surgery a retrospective cohort analysis.
      • Babazade R.
      • Yilmaz H.O.
      • Zimmerman N.M.
      • et al.
      Association between intraoperative low blood pressure and development of surgical site infection after colorectal surgery: a retrospective cohort study.
      • Hallqvist L.
      • Martensson J.
      • Granath F.
      • Sahlen A.
      • Bell M.
      Intraoperative hypotension is associated with myocardial damage in noncardiac surgery: an observational study.
      • van Waes J.A.R.
      • van Klei W.A.
      • Wijeysundera D.N.
      • Van Wolfswinkel L.
      • Lindsay T.F.
      • Beattie W.S.
      Association between intraoperative hypotension and myocardial injury after vascular surgery.
      • Mascha E.J.
      • Yang D.
      • Weiss S.
      • Sessler D.I.
      Intraoperative mean arterial pressure variability and 30-day mortality in patients having noncardiac surgery.
      • Pipanmekaporn T.
      • Punjasawadwong Y.
      • Charuluxananan S.
      • et al.
      Incidence of and risk factors for cardiovascular complications after thoracic surgery for noncancerous lesions.
      • Bijker J.B.
      • van Klei W.A.
      • Vergouwe Y.
      • et al.
      Intraoperative hypotension and 1-year mortality after noncardiac surgery.
      • Kheterpal S.
      • O’Reilly M.
      • Englesbe M.J.
      • et al.
      Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery.
      • White S.M.
      • Moppett I.K.
      • Griffiths R.
      • et al.
      Secondary analysis of outcomes after 11,085 hip fracture operations from the prospective UK Anaesthesia Sprint Audit of Practice (ASAP-2).
      • Brinkman R.
      • HayGlass K.T.
      • Mutch W.A.C.
      • Funk D.J.
      Acute kidney injury in patients undergoing open abdominal aortic aneurysm repair: a pilot observational trial.
      • Petsiti A.
      • Tassoudis V.
      • Vretzakis G.
      • et al.
      Depth of anesthesia as a risk factor for perioperative morbidity.
      • Marcantonio E.R.
      • Goldman L.
      • Orav E.J.
      • Cook E.F.
      • Thomas H.L.
      • Lee T.H.E.
      The association of intraoperative factors with the development of postoperative delirium.
      • Tallgren M.
      • Niemi T.
      • Pöyhiä R.
      • et al.
      Acute renal injury and dysfunction following elective abdominal aortic surgery.
      • House L.M.
      • Marolen K.N.
      • St Jacques P.J.
      • McEvoy M.D.
      • Ehrenfeld J.M.
      Surgical Apgar score is associated with myocardial injury after noncardiac surgery.
      • Sessler D.I.
      • Sigl J.C.
      • Kelley S.D.
      • et al.
      Hospital stay and mortality are increased in patients having a triple low of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia.
      • Sabaté S.
      • Mases A.
      • Guilera N.
      • et al.
      Incidence and predictors of major perioperative adverse cardiac and cerebrovascular events in non-cardiac surgery.
      • Taffé P.
      • Sicard N.
      • Pittet V.
      • Pichard S.
      • Burnand B.
      The occurrence of intra-operative hypotension varies between hospitals: observational analysis of more than 147,000 anaesthesia.
      • Sirivatanauksorn Y.
      • Parakonthun T.
      • Premasathian N.
      • et al.
      Renal dysfunction after orthotopic liver transplantation.
      • Tassoudis V.
      • Vretzakis G.
      • Petsiti A.
      • et al.
      Impact of intraoperative hypotension on hospital stay in major abdominal surgery.
      • Stapelfeldt W.H.
      • Yuan H.
      • Dryden J.K.
      • et al.
      The SLUScore: a novel method for detecting hazardous hypotension in adult patients undergoing noncardiac surgical procedures.
      • Jiang X.
      • Chen D.
      • Lou Y.
      • Li Z.
      Risk factors for postoperative delirium after spine surgery in middle- and old-aged patients.
      • Yang L.
      • Sun D.F.
      • Han J.
      • Liu R.
      • Wang L.J.
      • Zhang Z.Z.
      Effects of intraoperative hemodynamics on incidence of postoperative delirium in elderly patients: a retrospective study.
      • Yue J.
      • Luo Z.
      • Guo D.
      • et al.
      Evaluation of acute kidney injury as defined by the risk, injury, failure, loss, and end-stage criteria in critically ill patients undergoing abdominal aortic aneurysm repair.
      • Franck M.
      • Radtke F.M.
      • Prahs C.
      • et al.
      Documented intraoperative hypotension according to the three most common definitions does not match the application of antihypotensive medication.
      • Patti R.
      • Saitta M.
      • Cusumano G.
      • Termine G.
      • Di Vita G.
      Risk factors for postoperative delirium after colorectal surgery for carcinoma.
      • Vasivej T.
      • Sathirapanya P.
      • Kongkamol C.
      Incidence and risk factors of perioperative stroke in noncardiac, and nonaortic and its major branches surgery.
      • Thakar C.V.
      • Kharat V.
      • Blanck S.
      • Leonard A.C.
      Acute kidney injury after gastric bypass surgery.
      • Barone J.E.
      • Bull M.B.
      • Cussatti E.H.
      • Miller K.D.
      • Tucker J.B.
      Perioperative myocardial infarction in low-risk patients undergoing noncardiac surgery is associated with Intraoperative hypotension.
      • Lima E.Q.
      • Zanetta D.M.T.
      • Castro I.
      • et al.
      Risk factors for development of acute renal failure after liver transplantation.
      • Nakamura K.
      • Matsuyama M.
      • Yano M.
      • et al.
      Open surgery or stent repair for descending aortic diseases: results and risk factor analysis.
      • Davidovic L.B.
      • Maksic M.
      • Koncar I.
      • Ilic N.
      Open repair of AAA in a high volume center.
      • Sharma S.K.
      • McCauley R.
      • Cottam D.
      • et al.
      Acute changes in renal function after laparoscopic gastric surgery for morbid obesity.
      Commonly reported baseline characteristics were summarised by calculating weighted means of medians across study groups for each variable (Table 2). Two reviewers (E.M.W. and H.M.T.) independently assessed the methodological quality of the included articles. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
      • von Elm E.
      • Altman D.G.
      • Egger M.
      • et al.
      Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
      criteria and Consolidated Standards of Reporting Trials (CONSORT)
      • Schulz K.F.
      • Altman D.G.
      • Moher D.
      Group C. CONSORT 2010 statement : updated guidelines for reporting parallel group randomised trials.
      criteria were adapted and used for the composition of a checklist with predefined quality criteria. These criteria focus on the internal validity, external validity, bias, and precision (Supplementary Table S1). In short, all criteria on study design were scored as positive (+), negative (–), unclear (?), or not applicable (NA). The latter option was used when the criterion was not appropriate for the specific study design, such as loss-to-follow-up for a case–control study. Depending on the type of study design, a maximum of 13 ‘positive’ items (case–control studies), 14 items (randomised clinical trials; RCTs), or 15 items (cohort studies) could be assigned (Table 1, Supplementary Table S1). Disagreements between both reviewers were discussed. In case of persistent disagreement, the third reviewer made the final decision. Whereas the maximum score depended on study type, normalisation was achieved by calculating the quality score, defined as the number of positive items divided by the maximum number of items for that study type and expressed as a percentage.
      Table 1Results of the methodological assessment of studies on intraoperative hypotension and postoperative adverse outcomes. Scoring system to obtain a quality score for every included article based on 15 categories as described in Supplementary Table S1. +, if sufficient information is available and positive assessment; –, if insufficient information or negative assessment; ?, unknown; NA, not applicable. Depending on the type of study design, a maximum of 13 points (case–control studies), 14 points (randomised controlled trials, RCTs) or 15 points (cohort studies) were assigned
      First author (yr)refDesignABCDEFGHIJKLMNOQuality score (%)
      Hirsch (2015)
      • Hirsch J.
      • DePalma G.
      • Tsai T.T.
      • Sands L.P.
      • Leung J.M.
      Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery.
      Cohort+++++++++++++++15 (100)
      Monk (2015)
      • Monk T.G.
      • Bronsert M.R.
      • Henderson W.G.
      • et al.
      Association between intraoperative hypotension and hypertension and 30-day postoperative mortality in noncardiac surgery.
      Cohort++++++++++?++++14 (93)
      Willingham (2015)
      • Willingham M.D.
      • Karren E.
      • Shanks A.M.
      • et al.
      Concurrence of intraoperative hypotension, low minimum alveolar concentration, and low bispectral index is associated with postoperative death.
      Cohort+++++++++++?+++14 (93)
      Bijker (2012)
      • Bijker J.B.
      • Persoon S.
      • Peelen L.
      • et al.
      Intraoperative hypotension and perioperative ischemic stroke after general surgery.
      Case–control++++NANA++++++++12 (92)
      Mizota (2017)
      • Mizota T.
      • Hamada M.
      • Segawa H.
      Relationship between intraoperative hypotension and acute kidney injury after living donor liver transplantation: a retrospective analysis.
      Cohort+++++++++++++13 (87)
      Sun (2015)
      • Sun L.Y.
      • Wijeysundera D.N.
      • Tait G.A.
      • Beattie W.S.
      Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery.
      Cohort++++++++++?+++13 (87)
      Schmid (2016)
      • Schmid S.
      • Kapfer B.
      • Heim M.
      • et al.
      Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial.
      RCT++++++++NA++++12 (86)
      Roshanov (2017)
      • Roshanov P.S.
      • Rochwerg B.
      • Patel A.
      • et al.
      Enzyme inhibitors or angiotensin II receptor blockers.
      Cohort+++++++++++++12 (80)
      Salmasi (2017)
      • Salmasi V.
      • Maheshwari K.
      • Dongsheng Y.
      • et al.
      Thresholds, and acute kidney and myocardial injury after noncardiac surgery a retrospective cohort analysis.
      Cohort++++++++++++12 (80)
      Babazade (2016)
      • Babazade R.
      • Yilmaz H.O.
      • Zimmerman N.M.
      • et al.
      Association between intraoperative low blood pressure and development of surgical site infection after colorectal surgery: a retrospective cohort study.
      Cohort+++++++++?+++12 (80)
      Hallqvist (2016)
      • Hallqvist L.
      • Martensson J.
      • Granath F.
      • Sahlen A.
      • Bell M.
      Intraoperative hypotension is associated with myocardial damage in noncardiac surgery: an observational study.
      Cohort++++++++++++12 (80)
      Van Waes (2016)
      • van Waes J.A.R.
      • van Klei W.A.
      • Wijeysundera D.N.
      • Van Wolfswinkel L.
      • Lindsay T.F.
      • Beattie W.S.
      Association between intraoperative hypotension and myocardial injury after vascular surgery.
      Cohort+++++++++?+++12 (80)
      Mascha (2015)
      • Mascha E.J.
      • Yang D.
      • Weiss S.
      • Sessler D.I.
      Intraoperative mean arterial pressure variability and 30-day mortality in patients having noncardiac surgery.
      Cohort++++++?+++?+++12 (80)
      Pipanmekaporn (2014)
      • Pipanmekaporn T.
      • Punjasawadwong Y.
      • Charuluxananan S.
      • et al.
      Incidence of and risk factors for cardiovascular complications after thoracic surgery for noncancerous lesions.
      Cohort++++?+++++?+++12 (80)
      Walsh (2013)
      • Walsh M.
      • Devereaux P.J.
      • Garg A.X.
      • et al.
      Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension.
      Cohort+++++++++?+++12 (80)
      Bijker (2009)
      • Bijker J.B.
      • van Klei W.A.
      • Vergouwe Y.
      • et al.
      Intraoperative hypotension and 1-year mortality after noncardiac surgery.
      Cohort+++++++++?+++12 (80)
      Kheterpal (2009)
      • Kheterpal S.
      • O’Reilly M.
      • Englesbe M.J.
      • et al.
      Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery.
      Cohort+++++++++?+++12 (80)
      Monk (2005)
      • Monk T.G.
      • Saini V.
      • Weldon B.C.
      • Sigl J.C.
      Anesthetic management and one-year mortality after noncardiac surgery.
      Cohort+++++?+++++++12 (80)
      White (2016)
      • White S.M.
      • Moppett I.K.
      • Griffiths R.
      • et al.
      Secondary analysis of outcomes after 11,085 hip fracture operations from the prospective UK Anaesthesia Sprint Audit of Practice (ASAP-2).
      Cohort+++++++++?++11 (73)
      Brinkman (2015)
      • Brinkman R.
      • HayGlass K.T.
      • Mutch W.A.C.
      • Funk D.J.
      Acute kidney injury in patients undergoing open abdominal aortic aneurysm repair: a pilot observational trial.
      Cohort+++++?++++++11 (73)
      Petsiti (2015)
      • Petsiti A.
      • Tassoudis V.
      • Vretzakis G.
      • et al.
      Depth of anesthesia as a risk factor for perioperative morbidity.
      Cohort++++++++?+++11 (73)
      Marcantonio (1998)
      • Marcantonio E.R.
      • Goldman L.
      • Orav E.J.
      • Cook E.F.
      • Thomas H.L.
      • Lee T.H.E.
      The association of intraoperative factors with the development of postoperative delirium.
      Cohort++++++?++0?++11 (73)
      Tallgren (2007)
      • Tallgren M.
      • Niemi T.
      • Pöyhiä R.
      • et al.
      Acute renal injury and dysfunction following elective abdominal aortic surgery.
      RCT++++?++NA++++10 (71)
      House (2016)
      • House L.M.
      • Marolen K.N.
      • St Jacques P.J.
      • McEvoy M.D.
      • Ehrenfeld J.M.
      Surgical Apgar score is associated with myocardial injury after noncardiac surgery.
      Cohort+++++++?+++10 (67)
      Sessler (2012)
      • Sessler D.I.
      • Sigl J.C.
      • Kelley S.D.
      • et al.
      Hospital stay and mortality are increased in patients having a triple low of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia.
      Cohort++++??++++?++10 (67)
      Sabaté (2011)
      • Sabaté S.
      • Mases A.
      • Guilera N.
      • et al.
      Incidence and predictors of major perioperative adverse cardiac and cerebrovascular events in non-cardiac surgery.
      Cohort++++??+++?+++10 (67)
      Taffé (2009)
      • Taffé P.
      • Sicard N.
      • Pittet V.
      • Pichard S.
      • Burnand B.
      The occurrence of intra-operative hypotension varies between hospitals: observational analysis of more than 147,000 anaesthesia.
      Cohort+++++??++?+++10 (67)
      Sirivatanauksorn (2014)
      • Sirivatanauksorn Y.
      • Parakonthun T.
      • Premasathian N.
      • et al.
      Renal dysfunction after orthotopic liver transplantation.
      Cohort+++++?++?++9 (60)
      Tassoudis (2011)
      • Tassoudis V.
      • Vretzakis G.
      • Petsiti A.
      • et al.
      Impact of intraoperative hypotension on hospital stay in major abdominal surgery.
      Cohort+++++?++?++9 (60)
      Stapelfeldt (2017)
      • Stapelfeldt W.H.
      • Yuan H.
      • Dryden J.K.
      • et al.
      The SLUScore: a novel method for detecting hazardous hypotension in adult patients undergoing noncardiac surgical procedures.
      Cohort+++?+++++8 (53)
      Jiang (2016)
      • Jiang X.
      • Chen D.
      • Lou Y.
      • Li Z.
      Risk factors for postoperative delirium after spine surgery in middle- and old-aged patients.
      Cohort++++?++++8 (53)
      Yang (2016)
      • Yang L.
      • Sun D.F.
      • Han J.
      • Liu R.
      • Wang L.J.
      • Zhang Z.Z.
      Effects of intraoperative hemodynamics on incidence of postoperative delirium in elderly patients: a retrospective study.
      Cohort+++++++7 (47)
      Yue (2013)
      • Yue J.
      • Luo Z.
      • Guo D.
      • et al.
      Evaluation of acute kidney injury as defined by the risk, injury, failure, loss, and end-stage criteria in critically ill patients undergoing abdominal aortic aneurysm repair.
      Cohort+++??+?+++7 (47)
      Franck (2011)
      • Franck M.
      • Radtke F.M.
      • Prahs C.
      • et al.
      Documented intraoperative hypotension according to the three most common definitions does not match the application of antihypotensive medication.
      Cohort+++??++?++7 (47)
      Patti (2011)
      • Patti R.
      • Saitta M.
      • Cusumano G.
      • Termine G.
      • Di Vita G.
      Risk factors for postoperative delirium after colorectal surgery for carcinoma.
      Cohort+++??+?+++7 (47)
      Vasivej (2016)
      • Vasivej T.
      • Sathirapanya P.
      • Kongkamol C.
      Incidence and risk factors of perioperative stroke in noncardiac, and nonaortic and its major branches surgery.
      Case–control+++NANA+?++6 (46)
      Thakar (2007)
      • Thakar C.V.
      • Kharat V.
      • Blanck S.
      • Leonard A.C.
      Acute kidney injury after gastric bypass surgery.
      Cohort+??++?+++6 (40)
      Barone (2002)
      • Barone J.E.
      • Bull M.B.
      • Cussatti E.H.
      • Miller K.D.
      • Tucker J.B.
      Perioperative myocardial infarction in low-risk patients undergoing noncardiac surgery is associated with Intraoperative hypotension.
      Case–control+NANA++?++5 (38)
      Lima (2003)
      • Lima E.Q.
      • Zanetta D.M.T.
      • Castro I.
      • et al.
      Risk factors for development of acute renal failure after liver transplantation.
      Cohort++?++?+5 (33)
      Nakamura (2009)
      • Nakamura K.
      • Matsuyama M.
      • Yano M.
      • et al.
      Open surgery or stent repair for descending aortic diseases: results and risk factor analysis.
      Case–control+NANA+?++4 (31)
      Davidovic (2017)
      • Davidovic L.B.
      • Maksic M.
      • Koncar I.
      • Ilic N.
      Open repair of AAA in a high volume center.
      Cohort++?++4 (27)
      Sharma (2006)
      • Sharma S.K.
      • McCauley R.
      • Cottam D.
      • et al.
      Acute changes in renal function after laparoscopic gastric surgery for morbid obesity.
      Case–control??+?++3 (23)
      Table 2Summary of the patient, surgery and hypotension characteristics of each study. Continuous variables are expressed as mean (sd) or x (x∼x) = mean (range) or x (x-x) = median (interquartile range). Categorical variables are expressed as xx% body mass index or weight (W) is expressed as kg m−2 or kg. Any definition of history of arrhythmia or renal dysfunction was included. If available, renal dysfunction was expressed as serum creatinine in μmol l−1. –, not available; *, values are the weighted mean values of the study groups; †, median (10th–90th percentile). a-, absolute threshold expressed as mm Hg; AR, achievement rate; AUT, area under the threshold; BP blood pressure; CAD, coronary artery disease; Cr, creatinine; CVD, cerebrovascular disease; DBP, diastolic blood pressure; Di, dichotomous; DM, diabetes mellitus; Du, duration under a blood pressure threshold; eGFR, estimated glomerular filtration rate; Gen. anaesth., general anaesthesia; GI, gastro-intestinal; HT, hypertension; LiverTX, liver transplantation; Low, lowest blood pressure; MAP, mean blood pressure; MI, myocardial injury; r-, relative threshold expressed as percentage decrease from baseline BP; RCRI, Revised Cardiac Risk Index; SAS, blood pressure as part of Surgical Apgar Score; SBP, systolic blood pressure; TIA, transient ischaemic attack; TL, triple low; TWA, time-weighted average; V, blood pressure variance; Var, variability or variance
      StudiesPatient characteristicsComorbidity (%)Procedure characteristics (%)Intraoperative hypotension
      First authorTotalAgeSexASAStrokeHTDMCADRenal diseaseGen. anaesth.Length of surgeryEmergency surgeryType of surgeryBP threshold typeThresholdAnalysis
      (yr)n(yr)F, %1234anyminmost frequent
      Hirsch (2015)
      • Hirsch J.
      • DePalma G.
      • Tsai T.T.
      • Sands L.P.
      • Leung J.M.
      Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery.
      59474 (6)5148471300 (144)0Orthopaedic 53rSBP, rMAP, aMAP↓ >10–40%, <50 mm HgDu, Var
      Monk (2015)
      • Monk T.G.
      • Bronsert M.R.
      • Henderson W.G.
      • et al.
      Association between intraoperative hypotension and hypertension and 30-day postoperative mortality in noncardiac surgery.
      18 75660 (13)7326581319120 (72–186)8General 32aSBP<80 mm HgDu
      Willingham (2015)
      • Willingham M.D.
      • Karren E.
      • Shanks A.M.
      • et al.
      Concurrence of intraoperative hypotension, low minimum alveolar concentration, and low bispectral index is associated with postoperative death.
      13 19856 (44–66)479393516any: 3481720100178 (115–259)aMAP, TL<75mm HgDu
      Bijker (2012)*,
      • Bijker J.B.
      • Persoon S.
      • Peelen L.
      • et al.
      Intraoperative hypotension and perioperative ischemic stroke after general surgery.
      48 241 (42/252)66 (57–76)4068323869163 (130–232)Vascular 48aSBP, aMAP, rSBP, rMAP<100–70 mm Hg, <70–40 mm Hg, ↓ >10–40%Du
      Mizota (2017)*,
      • Mizota T.
      • Hamada M.
      • Segawa H.
      Relationship between intraoperative hypotension and acute kidney injury after living donor liver transplantation: a retrospective analysis.
      23154 (44–60)511922100838 (752–960)LiverTX 100aMAP<40,<50 mm HgDu, Di
      Sun (2015)*,
      • Sun L.Y.
      • Wijeysundera D.N.
      • Tait G.A.
      • Beattie W.S.
      Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery.
      512761 (14)53any: 248151116>120: 790General 26aMAP<65, <60, <55 mm HgDu
      Schmid (2016)*,
      • Schmid S.
      • Kapfer B.
      • Heim M.
      • et al.
      Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial.
      18066 (12)2356206100100Abdominal 100aMAP>70 mm HgAR
      Roshanov (2017)
      • Roshanov P.S.
      • Rochwerg B.
      • Patel A.
      • et al.
      Enzyme inhibitors or angiotensin II receptor blockers.
      14 68765 (12)527471912eGFR: 79 (23)14Orthopaedic 20aSBP<90 mm HgDi
      Salmasi (2017)*,
      • Salmasi V.
      • Maheshwari K.
      • Dongsheng Y.
      • et al.
      Thresholds, and acute kidney and myocardial injury after noncardiac surgery a retrospective cohort analysis.
      57 31556 (15)56238547349171225(121)4Abdominal 23aMAP, rMAP<80–40 mm Hg, ↓>10–60%Du, TWA
      Babazade (2016)
      • Babazade R.
      • Yilmaz H.O.
      • Zimmerman N.M.
      • et al.
      Association between intraoperative low blood pressure and development of surgical site infection after colorectal surgery: a retrospective cohort study.
      252156 (15)454550542144100199 (142–265)1Colorectal 100aSBP, aMAP<80mm Hg, <55mm HgDu
      Hallqvist (2016)
      • Hallqvist L.
      • Martensson J.
      • Granath F.
      • Sahlen A.
      • Bell M.
      Intraoperative hypotension is associated with myocardial damage in noncardiac surgery: an observational study.
      30067 (57–74)531046430.3438390Abdominal 40rSBP↓ >50%, >5 minDi
      van Waes (2016)*,
      • van Waes J.A.R.
      • van Klei W.A.
      • Wijeysundera D.N.
      • Van Wolfswinkel L.
      • Lindsay T.F.
      • Beattie W.S.
      Association between intraoperative hypotension and myocardial injury after vascular surgery.
      89074 (8)31114364921108100191 (108)30(T)EVAR 24aMAP<50, <60 mm Hg, ↓>30%, ↓ >40%Du, (AUT)
      Mascha (2015)*,
      • Mascha E.J.
      • Yang D.
      • Weiss S.
      • Sessler D.I.
      Intraoperative mean arterial pressure variability and 30-day mortality in patients having noncardiac surgery.
      104 40157 (18)5354047814817146174 (114–252)5aMAP<80–50 mm HgDu, TWA, Var
      Pipanmekaporn (2014)*,
      • Pipanmekaporn T.
      • Punjasawadwong Y.
      • Charuluxananan S.
      • et al.
      Incidence of and risk factors for cardiovascular complications after thoracic surgery for noncancerous lesions.
      71949 (16)291458281810210100142 (65)46Thoracic 100aSBP, aMAP<80 or <60 mm Hg, >15 minDi
      Walsh (2013)*,
      • Walsh M.
      • Devereaux P.J.
      • Garg A.X.
      • et al.
      Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension.
      33 33056 (16)50240508513eGFR: 93 (27)7aMAP<75–55 mm HgDu
      Bijker (2009)
      • Bijker J.B.
      • van Klei W.A.
      • Vergouwe Y.
      • et al.
      Intraoperative hypotension and 1-year mortality after noncardiac surgery.
      170552 (16)483851117228any: 1588112 (73–163)0General 88aSBP, rSBP, aMAP, rMAP<100–70 mm Hg, ↓ >10–40%, <70-40 mm Hg, ↓ >10–40%Du
      Kheterpal (2009)*,
      • Kheterpal S.
      • O’Reilly M.
      • Englesbe M.J.
      • et al.
      Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery.
      7740≥68: 2349any: 5401338812aSBP, aMAP, rSBP, rMAP<80–70 mm Hg, <60–50 mm Hg, ↓ >30–40%Di?
      Monk (2005)
      • Monk T.G.
      • Saini V.
      • Weldon B.C.
      • Sigl J.C.
      Anesthetic management and one-year mortality after noncardiac surgery.
      106451 (37–65)6413523543346100186 (138–258)Orthopaedic 26aSBP<80 mm HgDu
      White (2016)
      • White S.M.
      • Moppett I.K.
      • Griffiths R.
      • et al.
      Secondary analysis of outcomes after 11,085 hip fracture operations from the prospective UK Anaesthesia Sprint Audit of Practice (ASAP-2).
      11 08583 (24–104)723305512115571454Hip surgery 100aSBP, aMAPLowest BPLow
      Brinkman (2015)*,
      • Brinkman R.
      • HayGlass K.T.
      • Mutch W.A.C.
      • Funk D.J.
      Acute kidney injury in patients undergoing open abdominal aortic aneurysm repair: a pilot observational trial.
      4069 (9)356813100228 (84)0Aorta 100aMAP<65 mm HgAUT
      Petsiti (2015)
      • Petsiti A.
      • Tassoudis V.
      • Vretzakis G.
      • et al.
      Depth of anesthesia as a risk factor for perioperative morbidity.
      24864 (11)48321471383100232 (55)0Abdominal 100aMAP, rMAP<60 or <70 mm Hg +

      ↓ >30%
      Di
      Marcantonio (1998)
      • Marcantonio E.R.
      • Goldman L.
      • Orav E.J.
      • Cook E.F.
      • Thomas H.L.
      • Lee T.H.E.
      The association of intraoperative factors with the development of postoperative delirium.
      134167 (9)55Orthopaedic 43aSBP or rSBP<90 mm Hg or ↓ >33%Di
      Tallgren (2007)*,
      • Tallgren M.
      • Niemi T.
      • Pöyhiä R.
      • et al.
      Acute renal injury and dysfunction following elective abdominal aortic surgery.
      6967 (60–74)22667431000Aorta 100aMAP<65 mm Hg, >15 minDi
      House (2016)*,
      • House L.M.
      • Marolen K.N.
      • St Jacques P.J.
      • McEvoy M.D.
      • Ehrenfeld J.M.
      Surgical Apgar score is associated with myocardial injury after noncardiac surgery.
      46 79954 (13)4741343164162 (108)4aMAP<40 mm HgDi/SAS
      Sessler (2012)
      • Sessler D.I.
      • Sigl J.C.
      • Kelley S.D.
      • et al.
      Hospital stay and mortality are increased in patients having a triple low of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia.
      24 120100aMAP, TL<70 mm HgDu
      Sabaté (2011)
      • Sabaté S.
      • Mases A.
      • Guilera N.
      • et al.
      Incidence and predictors of major perioperative adverse cardiac and cerebrovascular events in non-cardiac surgery.
      338767 (47–81)†52855334RCRI ≥3: 761120 (60–248)†7Orthopaedic 34aSBP or aMAP/rMAP<100 mm Hg or ↓ >20 mm Hg/20%, >60 minDi
      Taffé (2009)*,
      • Taffé P.
      • Sicard N.
      • Pittet V.
      • Pichard S.
      • Burnand B.
      The occurrence of intra-operative hypotension varies between hospitals: observational analysis of more than 147,000 anaesthesia.
      147 57355 (18)56274822367104 (?–?)20rMAP↓ >30%, >10 minDi
      Sirivatanauksorn (2014)*,
      • Sirivatanauksorn Y.
      • Parakonthun T.
      • Premasathian N.
      • et al.
      Renal dysfunction after orthotopic liver transplantation.
      8153 (23–70)31Cr: 90 (38–168)100276 (168–438)LiverTX 100aMAP<70 mm Hg, >30 minDi
      Tassoudis (2011)
      • Tassoudis V.
      • Vretzakis G.
      • Petsiti A.
      • et al.
      Impact of intraoperative hypotension on hospital stay in major abdominal surgery.
      10062 (14)47321461283100195 (71)0Abdominal 100aMAP, rMAP<60 or

      <70mm Hg + ↓ >30%
      Di
      Stapelfeldt (2017)
      • Stapelfeldt W.H.
      • Yuan H.
      • Dryden J.K.
      • et al.
      The SLUScore: a novel method for detecting hazardous hypotension in adult patients undergoing noncardiac surgical procedures.
      152 445179 (118–259)90aMAP<75–45 mm HgDu
      Jiang (2016)*,
      • Jiang X.
      • Chen D.
      • Lou Y.
      • Li Z.
      Risk factors for postoperative delirium after spine surgery in middle- and old-aged patients.
      45165 (18)501461100164 (62)Spine 100aSBP<80 mm HgDi
      Yang (2016)*,
      • Yang L.
      • Sun D.F.
      • Han J.
      • Liu R.
      • Wang L.J.
      • Zhang Z.Z.
      Effects of intraoperative hemodynamics on incidence of postoperative delirium in elderly patients: a retrospective study.
      48081 (6)517129433043100188 (32)0r?BP↓ >30%Di
      Yue (2013)*,
      • Yue J.
      • Luo Z.
      • Guo D.
      • et al.
      Evaluation of acute kidney injury as defined by the risk, injury, failure, loss, and end-stage criteria in critically ill patients undergoing abdominal aortic aneurysm repair.
      71>70: 3721112310038Aorta 100aSBP/aMAP<↓ 30/<65 mm HgDi
      Franck (2011)*,
      • Franck M.
      • Radtke F.M.
      • Prahs C.
      • et al.
      Documented intraoperative hypotension according to the three most common definitions does not match the application of antihypotensive medication.
      235053 (41–65)50505010098 (63–148)aSBP, rSBP<100 or

      ↓>30%, <92 mm Hg, <80 mm Hg, ↓ >20%
      Di
      Patti (2011)*,
      • Patti R.
      • Saitta M.
      • Cusumano G.
      • Termine G.
      • Di Vita G.
      Risk factors for postoperative delirium after colorectal surgery for carcinoma.
      10070 (3)609412921100121 (24)0Abdominal 100aMAP≤60mm HgDi
      Vasivej (2016)*,
      • Vasivej T.
      • Sathirapanya P.
      • Kongkamol C.
      Incidence and risk factors of perioperative stroke in noncardiac, and nonaortic and its major branches surgery.
      55 648 (42/168)58 (14)5264327233959153 (78–244)7aMAP<65 mm HgDi
      Thakar (2007)*,
      • Thakar C.V.
      • Kharat V.
      • Blanck S.
      • Leonard A.C.
      Acute kidney injury after gastric bypass surgery.
      50443 (10)83572641000Abdominal 100aMAP<60 mm HgDi
      Barone (2002)*,
      • Barone J.E.
      • Bull M.B.
      • Cussatti E.H.
      • Miller K.D.
      • Tucker J.B.
      Perioperative myocardial infarction in low-risk patients undergoing noncardiac surgery is associated with Intraoperative hypotension.
      25 50174 (11)45Mean ASA: 2.94019any: 30124 (55)27aSBP<100 mm Hg, >10 minDi
      Lima (2003)*,
      • Lima E.Q.
      • Zanetta D.M.T.
      • Castro I.
      • et al.
      Risk factors for development of acute renal failure after liver transplantation.
      9244 (14)48Cr: 88 (35)100LiverTX 100aMAP<60 mm HgDi
      Nakamura (2009)*,
      • Nakamura K.
      • Matsuyama M.
      • Yano M.
      • et al.
      Open surgery or stent repair for descending aortic diseases: results and risk factor analysis.
      7271 (10)29any: 15887any: 191115Aorta 100aSBP<70 mm HgDi
      Davidovic (2017)
      • Davidovic L.B.
      • Maksic M.
      • Koncar I.
      • Ilic N.
      Open repair of AAA in a high volume center.
      45066 (7)127026111000%Aorta 100%aSBP<100 mm HgDi
      Sharma (2006)*,
      • Sharma S.K.
      • McCauley R.
      • Cottam D.
      • et al.
      Acute changes in renal function after laparoscopic gastric surgery for morbid obesity.
      180043 (9)8057222100223 (63)0%Abdominal 100%aSBP<100 mm Hg, >5 minDi

       Reporting and aggregation of results

      For the reported strengths of association for absolute blood pressure thresholds and hypotension durations, multivariable associations from aetiological studies were presented when available; otherwise univariable strengths of associations were shown (Table 3). Strengths of associations were grouped according to (cumulative) durations of ≥1 min, ≥5 min, ≥10 min, and ≥20 min exposure to intraoperative hypotension below particular absolute thresholds. Studies that used a threshold that was relative to a baseline blood pressure were grouped with the absolute threshold that corresponded with the relative departure from the reported mean baseline blood pressure or a baseline of 140/90 mm Hg when no mean baseline was reported. For example, Hallqvist and colleagues
      • Hallqvist L.
      • Martensson J.
      • Granath F.
      • Sahlen A.
      • Bell M.
      Intraoperative hypotension is associated with myocardial damage in noncardiac surgery: an observational study.
      used a relative threshold of a 50% decrease in systolic blood pressure (SBP). As no mean baseline blood pressure was reported, the study was grouped with absolute thresholds SBP <70 mm Hg (50% of 140 mm Hg).
      Table 3Summary of reported and extrapolated strength of associations of mortality and organ injury in noncardiac patients. Grey cells represent statistically not significant results. Bold cells represent statistically significant results. Italic cells represent extrapolated results. *Adherence to dichotomous definition instead of an analysis of depth/duration of a certain threshold or continuous variable. Relative threshold. Based on combination relative and absolute threshold. Based on both relative and absolute threshold(s) analysed. §Exception of duration or time definition; Bijker (2009), hazard risk 1 yr mortality translated to 30 day mortality. ||Exception of hypotension definition or analysis; White (2016), odds ratio per mm Hg mean blood pressure decrease or per 5 mm Hg systolic blood pressure increase; Sessler (2012), single low (low MAP/high bispectral index/high mean alveolar concentration); Sabaté (2011), composite endpoint; Stapelfeldt (2017), odds ratio for percentage increase in the odds of the outcome per limit exceeded; Schmid (2016); regression coefficient for the achievement rate time spend with mean blood pressure >70 mm Hg compared with total surgery time; Monk (2015), odds ratio for systolic blood pressures 89–80 mm Hg, 79–70 mm Hg or 69–60 mm Hg for 2–4.9 min or >5 min, respectively. AK, Acute Kidney Injury Network definition (AKIN); Clin, diagnosis based on clinical signs and symptoms; Cr, creatinine concentration; CK-MB, creatinine-kinase-Mb concentration; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV); HR, hazard ratio; KD, Kidney Disease Improving Global Outcomes (KDIGO); NS, not significant; OR, odds ratio; RR, relative risk; RF, Risk, Injury, Failure, Loss and End-stage kidney disease classification (RIFLE); TnT, troponin T concentration; TOAST, Trial of ORG 10172 in Acute Stroke Treatment (TOAST).1
      Table thumbnail fx1a
      For studies that reported their strength of association per time-unit increase, the strengths of associations for other durations were estimated from the reported strengths of associations using the lower bound of the duration category. For example, Monk and colleagues
      • Monk T.G.
      • Saini V.
      • Weldon B.C.
      • Sigl J.C.
      Anesthetic management and one-year mortality after noncardiac surgery.
      reported a relative risk (RR) of 1.036 per min that SBP was <80 mm Hg. For the category SBP ≥ 5 min <80 mm Hg, the RR was then estimated by 1.0365=1.193.
      The reported strengths of associations were aggregated into single risk categories per blood pressure threshold and per hypotension duration for the five organ injury outcomes—mortality, AKI, MI, stroke, and delirium—and combined into an overall organ injury risk per threshold and duration (Table 4). For each category, the highest association [odds ratio (OR), RR, or hazard ratio (HR)] among the available evidence of sufficient quality was classified into a risk of mild, moderate, or high as defined below. Studies were considered qualitatively sufficient when they received a quality score ≥80% and defined an intraoperative hypotension analysis in their primary of secondary objectives. The highest organ injury risk for a specific blood pressure threshold and duration category was then considered to be the overall organ injury risk.
      Table 4Summary of highest strength of associations of association of mortality and organ injury in noncardiac patients translated to risk categories. *Not statistically significant; Hirsch (2015) performed a multivariable logistic regression model to analyse their data but did not report odds ratios, only P-values (P=0.409 for duration of mean blood pressure <50 mm Hg). HR, hazard ratio; MAP, mean blood pressure; OR, odds ratio; RR, relative risk.2
      Table thumbnail fx2
      Several additional assumptions and conversions were made to compare studies and their strengths of associations. First, strengths of associations that could not be converted to an OR, RR, or HR per blood pressure threshold and duration category were not considered in the risk categorisation summary. Second, ORs, RRs, and HRs were deemed interchangeable in their magnitude, as the outcome incidences were relatively low (the rare disease assumption). Third, the cut-off to classify a strength of association as high-risk was chosen as a ‘doubled risk’ or more (OR/RR/HRhigh≥2.0). The cut-off for moderate risk was chosen at half the high-risk cut-off on an exponential scale (√2=1.4≤OR/RR/HRmoderate<2.0), with the mild-risk category starting at a minimal increased risk (1.0<OR/RR/HRmild<1.4). Fourth, all blood pressure thresholds were converted to mean arterial pressure (MAP) equivalents based on a pulse pressure of 40 mm Hg (i.e. an SBP threshold <90 mm Hg represents a blood pressure of 90/50 mm Hg, which is comparable with a MAP threshold of <65 mm Hg). The 40 mm Hg pulse pressure was chosen because it was considered the most plausible pulse pressure across all reported systolic blood pressure thresholds. MAP was calculated by adding systolic blood pressure to two times diastolic blood pressure divided by three. Fifth, once a specific MAP threshold and hypotension duration reached a certain risk classification, that classification carried over to all subsequent lower MAP thresholds or longer hypotension durations at the same MAP threshold. This means that a moderate risk at MAP<60 mm Hg for acute kidney injury could not become a mild risk at MAP<55 mm Hg, nor could it become ‘no risk’ because no appropriate study reporting an association for that threshold was available. This reflects the assumption that lower blood pressures or longer intraoperative hypotension episodes always aggravate the risk of organ injury.

      Results

       Included studies

      Our search strategy yielded 5224 articles in total. After removal of duplicates (n=1955) and removing articles based on screening of title and abstract (n=3128), 131 abstracts adhered to the inclusion and exclusion criteria and the corresponding articles were retrieved (Fig. 1). After assessment of the full publications, 89 articles were excluded with the third reviewer adjudicating 10 of them. Eventually, 42 papers published between 2002 and 2017 were included for data extraction and quality assessment (Table 1). Eighteen studies (43%) had a quality score ≥80%, whereas the median quality score of the articles was 73% (interquartile range 49–80%; Table 1).
      Fig 1
      Fig 1Flow chart of search strategy and article selection of studies on intraoperative hypotension and postoperative adverse outcomes.
      Two observational substudies of randomised controlled trials (RCTs) were included in which postoperative effects of intraoperative hypotension were analysed. One RCT focused on goal-directed therapy during major abdominal surgery.
      • Schmid S.
      • Kapfer B.
      • Heim M.
      • et al.
      Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial.
      The other RCT investigated the efficacy of N-acetylcysteine in the prevention of acute kidney injury during elective abdominal aorta repair.
      • Tallgren M.
      • Niemi T.
      • Pöyhiä R.
      • et al.
      Acute renal injury and dysfunction following elective abdominal aortic surgery.
      In these two trials, both intervention arms were analysed for the association between intraoperative hypotension and AKI.

       Patient characteristics

      The number of included patients in the 42 included studies ranged from 40 to 152 445 (Table 2, panel ‘studies’),
      • Brinkman R.
      • HayGlass K.T.
      • Mutch W.A.C.
      • Funk D.J.
      Acute kidney injury in patients undergoing open abdominal aortic aneurysm repair: a pilot observational trial.
      • Stapelfeldt W.H.
      • Yuan H.
      • Dryden J.K.
      • et al.
      The SLUScore: a novel method for detecting hazardous hypotension in adult patients undergoing noncardiac surgical procedures.
      with a median of 1523 patients (inter-quartile range 261–17 739). In four studies (10%), the reported mean or median age was <50 yr and in seven studies the reported mean or median age was >70 yr (Table 2). Information about sex was reported in 40 studies. In 26 studies, the number of included females and males was comparable (40–60%), while in the remainder either males or females were overrepresented. Twenty-three studies (55%) provided information on the ASA physical status classification of the included patients (Table 2, panel ‘comorbidity’). In 36 studies (86%) any baseline information was reported on the occurrence of stroke, hypertension, diabetes, coronary artery disease or renal disease. In 15 (42%) of these 36 studies, information on at least four of these five conditions was reported. Twenty-six studies (72%) provided information on preoperative hypertension. In 22 of these 26 studies (85%), hypertension was found in ≥40% of the included patients. In 22 studies (52%) all patients underwent general anaesthesia, in one study <50% of the patients underwent general anaesthesia and 12 studies (24%) did not report any information on type of anaesthesia nor was it obvious from the included surgical procedures that it always had to be general anaesthesia. In several studies (n=12; 29%), large groups of patients underwent abdominal surgery, including liver transplantation (n=3 studies; 7%). Other frequent types of surgery were orthopaedic (n=7 studies; 17%) and vascular surgery (n=7 studies; 17%). In 11 studies (26%), no information was reported on type of surgery (Table 2, panel ‘procedure characteristics’).

       Intraoperative hypotension definitions

       Types of blood pressure thresholds

      In most studies, one or more hypotension definitions included a threshold based on absolute blood pressures (Table 2, panel ‘intraoperative hypotension’). Of the 42 studies, 29 (69%) used an intraoperative hypotension definition based on an absolute MAP threshold and 17 studies (40%) used hypotension definition based on an absolute SBP threshold. Seventeen (40%) studies used a hypotension definition based on a relative blood pressure threshold (a percentage-wise or absolute decrease from baseline blood pressure). In nine studies, relative MAP thresholds were used and in seven studies relative SBP thresholds were used. One study did not report whether their relative threshold was based on a mean or systolic arterial pressure.
      • Yang L.
      • Sun D.F.
      • Han J.
      • Liu R.
      • Wang L.J.
      • Zhang Z.Z.
      Effects of intraoperative hemodynamics on incidence of postoperative delirium in elderly patients: a retrospective study.

       Intraoperative hypotension duration

      Dichotomous analyses were performed in 20 studies (48%), of which seven (17%) included minimum time duration in their hypotension definition (Table 2, panel ‘intraoperative hypotension’). Fifteen studies (36%) performed a comparative analysis on whether the duration of hypotension was associated with any of the studied outcomes. Two studies (5%) analysed time as the duration in minutes below a blood pressure threshold. Two studies (5%) included an area under the threshold, and three studies (7%) used a different type of time-dependent analysis such as time-weighted average or percentage of the total procedure time. Four studies (10%) applied a different type of hypotension definition (e.g. lowest blood pressure, triple low conditions, or blood pressure as part of the Surgical Apgar Score). Fourteen studies reported associations for a minimum hypotension duration ≥1 min, eight studies ≥5 min, 12 studies ≥10 min, and seven studies ≥20 min.

       Blood pressure threshold values

      After ranking the included studies according to blood pressure threshold, quality score, and studied outcome, strengths of associations per threshold were compared (Table 3, panel ‘Intraoperative hypotension thresholds’). In addition, results based on a blood pressure threshold including duration were extrapolated to longer durations of hypotension. For each reported MAP threshold between ≤50 mm Hg and ≤75 mm Hg (5 mm Hg increments), from seven to twelve studies with MAP based thresholds were available. Six studies reported on MAP thresholds ≤40 mm Hg, ≤45 mm Hg and ≤80 mm Hg. There was no apparent relation between blood pressure threshold values and either quality score, intraoperative hypotension duration, or studied outcome.

       Studied outcomes

      Fourteen studies investigated mortality, with a follow-up duration between 1 day and 1 yr
      • Monk T.G.
      • Saini V.
      • Weldon B.C.
      • Sigl J.C.
      Anesthetic management and one-year mortality after noncardiac surgery.
      • Bijker J.B.
      • van Klei W.A.
      • Vergouwe Y.
      • et al.
      Intraoperative hypotension and 1-year mortality after noncardiac surgery.
      • Taffé P.
      • Sicard N.
      • Pittet V.
      • Pichard S.
      • Burnand B.
      The occurrence of intra-operative hypotension varies between hospitals: observational analysis of more than 147,000 anaesthesia.
      and an outcome incidence between 0.03% (follow-up: <1 day) and 5.6% (during hospital admission)
      • Taffé P.
      • Sicard N.
      • Pittet V.
      • Pichard S.
      • Burnand B.
      The occurrence of intra-operative hypotension varies between hospitals: observational analysis of more than 147,000 anaesthesia.
      • Nakamura K.
      • Matsuyama M.
      • Yano M.
      • et al.
      Open surgery or stent repair for descending aortic diseases: results and risk factor analysis.
      (Table 3, panel ‘Outcomes under study’). Twelve studies reported on associations between intraoperative hypotension and AKI. Follow-up duration varied between 1 day and 30 days,
      • Brinkman R.
      • HayGlass K.T.
      • Mutch W.A.C.
      • Funk D.J.
      Acute kidney injury in patients undergoing open abdominal aortic aneurysm repair: a pilot observational trial.
      • Lima E.Q.
      • Zanetta D.M.T.
      • Castro I.
      • et al.
      Risk factors for development of acute renal failure after liver transplantation.
      and incidence of AKI between 2.8% (7 days) and 72% (7 days).
      • White S.M.
      • Moppett I.K.
      • Griffiths R.
      • et al.
      Secondary analysis of outcomes after 11,085 hip fracture operations from the prospective UK Anaesthesia Sprint Audit of Practice (ASAP-2).
      • Sirivatanauksorn Y.
      • Parakonthun T.
      • Premasathian N.
      • et al.
      Renal dysfunction after orthotopic liver transplantation.
      Nine studies investigated myocardial injury or infarction, with a follow-up duration between 1 and 30 days.
      • Roshanov P.S.
      • Rochwerg B.
      • Patel A.
      • et al.
      Enzyme inhibitors or angiotensin II receptor blockers.
      • Hallqvist L.
      • Martensson J.
      • Granath F.
      • Sahlen A.
      • Bell M.
      Intraoperative hypotension is associated with myocardial damage in noncardiac surgery: an observational study.
      • Pipanmekaporn T.
      • Punjasawadwong Y.
      • Charuluxananan S.
      • et al.
      Incidence of and risk factors for cardiovascular complications after thoracic surgery for noncancerous lesions.
      The incidence of myocardial injury varied between 0.09% (in-hospital) and 30% (1 day).
      • Roshanov P.S.
      • Rochwerg B.
      • Patel A.
      • et al.
      Enzyme inhibitors or angiotensin II receptor blockers.
      • Barone J.E.
      • Bull M.B.
      • Cussatti E.H.
      • Miller K.D.
      • Tucker J.B.
      Perioperative myocardial infarction in low-risk patients undergoing noncardiac surgery is associated with Intraoperative hypotension.
      Stroke was reported in four studies, with incidences varying from 0.004% (in-hospital) to 0.09% (10 days).
      • Bijker J.B.
      • Persoon S.
      • Peelen L.
      • et al.
      Intraoperative hypotension and perioperative ischemic stroke after general surgery.
      • Sabaté S.
      • Mases A.
      • Guilera N.
      • et al.
      Incidence and predictors of major perioperative adverse cardiac and cerebrovascular events in non-cardiac surgery.
      Five studies reported on delirium with incidences between 9% (2 days) and 33% (5 days).
      • Hirsch J.
      • DePalma G.
      • Tsai T.T.
      • Sands L.P.
      • Leung J.M.
      Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery.
      • Marcantonio E.R.
      • Goldman L.
      • Orav E.J.
      • Cook E.F.
      • Thomas H.L.
      • Lee T.H.E.
      The association of intraoperative factors with the development of postoperative delirium.
      Another five studies reported on LOS, either prolonged LOS (three studies, incidences between 29.7% and 37%) or duration of LOS (two studies, median LOS between 4 and 7 days).

       Summary of evidence for the most reported outcomes

      Based on the methods described above, two studies with a high-quality score were not used for the determination of organ injury risks. The study of Roshanov and colleagues
      • Roshanov P.S.
      • Rochwerg B.
      • Patel A.
      • et al.
      Enzyme inhibitors or angiotensin II receptor blockers.
      was excluded because studying hypotension was not part of the primary or secondary research objectives. The strengths of associations reported by Schmid and colleagues
      • Schmid S.
      • Kapfer B.
      • Heim M.
      • et al.
      Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial.
      could not be converted into a comparable OR, RR, or HR as they reported a regression coefficient for the decrease of creatinine clearance (–0.28 ml min−1) per percent of total surgery time with MAP ≥70 mm Hg.
      The reported risks of any end-organ injury after noncardiac surgery started to increase with prolonged exposure (≥10 min) to MAPs <80 mm Hg, resulting in a mildly elevated risk, with OR/RR/HRs between 1.0 and 1.4 (Table 4). For shorter durations (<10 min), mildly elevated risks have been reported for thresholds of 70 mm Hg and lower. The reported risks increased to moderate (OR/RR/HRs between 1.4 and 2.0) with exposures to MAPs <65–60 mm Hg for ≥5 min, or any exposure <55–50 mm Hg. High risks (OR/RR/HRs >2.0) were reported for MAPs <65 mm Hg for ≥20 min, MAPs <50 mm Hg for ≥5 min, or any exposure <40 mm Hg.
      There were small differences between individual outcomes. For AKI and MI, the risks started at thresholds <65 mm Hg and increased gradually with degree and duration in a pattern that is largely similar between the two outcomes. For mortality, associations were reported for higher thresholds than AKI and MI, starting when there was prolonged exposure to MAP <80 mm Hg. The reported risks were mild for thresholds down to 55 mm Hg, at which the reported risks increased with prolonged exposures to MAP ≤55 mm Hg. For ischaemic stroke, only non-significant, small strengths of associations were reported. For delirium, non-significant associations were found for a duration of MAP <50 mm Hg. For LOS, insufficient data were available.

      Discussion

      This systematic review summarised the current literature as of March 2017 on the relation between intraoperative hypotension and postoperative outcomes. It provides an overview of blood pressures that were reported to be associated with inadequate organ perfusion. Prolonged exposure (≥10 min) to MAP <80 mm Hg and for shorter durations <70 mm Hg was associated with mildly elevated risks of any end-organ injury. Increased durations for MAP <65–60 mm Hg or for any exposure <55–50 mm Hg were associated with moderately or highly elevated risks.
      The interpretation and clinical applicability of the results of this review are hampered by the large differences between the studies and their observed associations. First, the included studies differed substantially in their selection of patient groups or procedures. Table 2 demonstrates that few studies are comparable in terms of baseline characteristics of the patients included. Further, the selection of surgical procedures ranged from very wide (e.g. noncardiac surgery) to very narrow (e.g. thoracic aortic aneurysm repair, gastric bypass surgery). Finally, there was also large variability in what patient and procedure characteristics were—or were not—reported by the various studies.
      Second, there was large variation in the way that intraoperative hypotension was defined and analysed. Definitions of hypotension across the studies included a wide range of degrees and durations for various types of blood pressure. Different thresholds were used for systolic, mean, or diastolic blood pressure, or even multiple thresholds were combined into a single definition. In addition to a threshold definition, the variable for hypotension can also be modelled in different ways.
      • Vernooij L.M.
      • van Klei W.A.
      • Machina M.
      • Pasma W.
      • Beattie W.S.
      • Peelen L.M.
      Different methods of modelling intraoperative hypotension and their association with postoperative complications in patients undergoing non-cardiac surgery.
      The thresholds often introduce a cut-off: anything above the threshold is considered to be the same (i.e. analysed as ‘zero’ or ‘no intraoperative hypotension’), even when the values are close to the threshold. However, everything below the threshold can be modelled in several ways: duration of blood pressure below the threshold, the area under the threshold, or simply a ‘one’ (i.e. ‘yes, the patient's blood pressure was below the threshold’).
      Third, there was important variation in the way that postoperative adverse outcomes were defined, analysed, and reported. Six different groups of postoperative adverse outcomes were reported as outcomes in this review: mortality, AKI, MI, ischaemic stroke, delirium, and LOS. Within each group different adverse outcomes with different definitions were studied. For example, the definition of myocardial injury ranged from only elevated biomarkers with or without ECG changes to cardiovascular complications. Residual confounding might have been present in studies that analysed postoperative cardiac or renal biomarkers drawn by clinical indication compared with routine postoperative biomarker measurements.
      • Walsh M.
      • Devereaux P.J.
      • Garg A.X.
      • et al.
      Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension.
      • Salmasi V.
      • Maheshwari K.
      • Dongsheng Y.
      • et al.
      Thresholds, and acute kidney and myocardial injury after noncardiac surgery a retrospective cohort analysis.
      • van Waes J.A.R.
      • van Klei W.A.
      • Wijeysundera D.N.
      • Van Wolfswinkel L.
      • Lindsay T.F.
      • Beattie W.S.
      Association between intraoperative hypotension and myocardial injury after vascular surgery.
      Furthermore, not all outcomes are interchangeable in their severity and incidence rates. Delirium might be an outcome more sensitive to find the low blood pressure threshold, but regarding severity and incidence rates it is not on par with mortality and AKI.
      The fourth issue is a result of the three issues mentioned before. The large heterogeneity in baseline characteristics, hypotension definitions, and studied outcomes made it challenging to come to a quantitative summary of the results. Hence, we made various conversions and assumptions on how to merge definitions of intraoperative hypotension and reported strengths of associations of these studies in a qualitative way. Additionally, we only used high quality studies (quality score ≥80%) with blood pressure thresholds converted to MAP thresholds for the organ-injury risk classification.
      Based on several assumptions and variations in patients, intraoperative hypotension definitions, outcome definitions, and analyses, it is still difficult to reliably define a common ‘cut-off’ for which blood pressure is too low. Although the risk of end-organ injury seems to increase rapidly with prolonged exposure to lower intraoperative blood pressures, based on current evidence, we cannot prove a causal relation between intraoperative blood pressures and outcomes. Current studies on intraoperative hypotension aim to answer: ‘What blood pressure is too low?’, but their data can only be used to answer ‘What blood pressure is associated with adverse outcomes given current treatment standards?’ In other words, this review does not address the question on what blood pressure thresholds result in organ hypoperfusion, but whether there is remaining hypoperfusion despite present routines to manage patients' blood pressures.
      All contributing factors and interactions are difficult to unravel and discriminate and it seems unlikely that we will be able to explore the contribution of separate factors using only observational data. Therefore, intervention studies—such as pragmatic trials—are required to understand the causal chain of intraoperative low blood pressure and adverse outcomes. After completion of the systematic search described in this review, three trials concerning intraoperative blood pressure manipulation have been published. In the first trial,
      • Sabaté S.
      • Mases A.
      • Guilera N.
      • et al.
      Incidence and predictors of major perioperative adverse cardiac and cerebrovascular events in non-cardiac surgery.
      elderly patients with chronic hypertension who underwent major abdominal surgery were randomised to one of three target MAP groups. Vasopressor therapy and a fluid management protocol based on stroke volume variation were used to adjust MAP. This study showed that a target MAP of 80–95 mm Hg, compared with lower (65–79 mm Hg) and higher targets (96–110 mm Hg) can decrease the incidence of AKI. Incidences of stroke and mortality did not significantly differ among groups. The lower incidence of AKI in the midrange MAP group compared with the lower MAP group is in accordance with results from observational studies (Table 4). Strict inclusion and exclusion criteria regarding age, comorbidities, and preoperative medication use limit generalisability of this trial.
      • Wu X.
      • Jiang Z.
      • Ying J.
      • Han Y.
      • Chen Z.
      Optimal blood pressure decreases acute kidney injury after gastrointestinal surgery in elderly hypertensive patients: a randomized study.
      In a second trial,
      • Futier E.
      • Lefrant J.-Y.
      • Guinot P.-G.
      • et al.
      Effect of individualized vs standard blood pressure management strategies on postoperative organ dysfunction among high-risk patients undergoing major surgery a randomized clinical trial.
      two blood pressure management strategies and their effects on postoperative organ dysfunction in patients undergoing major surgery were studied. This study showed that achieving a systolic blood pressure within 10% of the reference value by using continuous vasopressor infusion may prevent postoperative organ dysfunction compared with a strategy of only treating systolic blood pressures <80 mm Hg or <40% of the reference value (standard care). However, anticipation of an expected blood pressure decline was not allowed and the standard care group treatment thresholds might not really represent current clinical care. In a third trial,
      • McCormick P.J.
      • Levin M.A.
      • Lin H.
      • Sessler D.I.
      • Reich D.L.
      Effectiveness of an electronic alert for hypotension and low bispectral index on 90-day postoperative mortality.
      it was shown that avoidance of ‘double low’ events defined as MAP<75 mm Hg and bispectral index <45 by automated alerts, did not significantly decrease the 90-day mortality incidence in adults who underwent noncardiac surgery. In this study, no standardised blood pressure treatment protocols were used. Future studies on intraoperative hypotension should aim to explore blood pressure thresholds within specific patient groups and for specific outcomes. These should include other variables that are indicative of underlying causes and mechanisms of hypotension, such as heart rate, pulse pressure variation, cardiac output estimated by advanced techniques, and specific biomarkers. This will allow us to study mechanistic hypotheses that are outcome-specific and whether mechanism-specific interventions will improve outcomes.
      In conclusion, the reported associations suggest that organ injury might occur when the mean arterial pressure decreases <80 mm Hg for ≥10 min, and that this risk increases with blood pressures becoming progressively lower. Given the retrospective observational design of most studies, reflected by large variability in patient characteristics, hypotension definitions, and outcomes, solid conclusions on which blood pressures under which circumstances are truly too low cannot be drawn. We are in need of prospective interventional studies in specific patient groups and for specific outcomes to further unravel this topic.

      Authors' contributions

      Study concept and design: all authors.
      Acquisition of data: E.M.W., T.H.K., H.M.T.
      Interpretation of data: E.M.W., T.H.K., H.M.T., W.v.K.
      Drafting the manuscript: E.M.W., T.H.K., H.M.T.
      Critical revision of the manuscript for important intellectual content: all authors.
      Final approval of the version to be published: all authors.

      Declaration of interest

      None declared.

      Funding

      Departmental.

      Appendix A. Supplementary data

      The following are the supplementary data related to this article:

      References

        • Bijker J.B.
        • van Klei W.A.
        • Kappen T.H.
        • van Wolfswinkel L.
        • Moons K.G.M.
        • Kalkman C.J.
        Incidence of intraoperative hypotension as a function of the chosen definition: literature definitions applied to a retrospective cohort using automated data collection.
        Anesthesiology. 2007; 107: 213-220
        • Monk T.G.
        • Saini V.
        • Weldon B.C.
        • Sigl J.C.
        Anesthetic management and one-year mortality after noncardiac surgery.
        Anesth Analg. 2005; 100: 4-10
        • Sun L.Y.
        • Wijeysundera D.N.
        • Tait G.A.
        • Beattie W.S.
        Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery.
        Anesthesiology. 2015; 123: 515-523
        • Walsh M.
        • Devereaux P.J.
        • Garg A.X.
        • et al.
        Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension.
        Anesthesiology. 2013; 119: 507-515
        • Hirsch J.
        • DePalma G.
        • Tsai T.T.
        • Sands L.P.
        • Leung J.M.
        Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery.
        Br J Anaesth. 2015; 115: 418-426
        • Monk T.G.
        • Bronsert M.R.
        • Henderson W.G.
        • et al.
        Association between intraoperative hypotension and hypertension and 30-day postoperative mortality in noncardiac surgery.
        Anesthesiology. 2015; 123: 307-319
        • Willingham M.D.
        • Karren E.
        • Shanks A.M.
        • et al.
        Concurrence of intraoperative hypotension, low minimum alveolar concentration, and low bispectral index is associated with postoperative death.
        Anesthesiology. 2015; 123: 775-785
        • Bijker J.B.
        • Persoon S.
        • Peelen L.
        • et al.
        Intraoperative hypotension and perioperative ischemic stroke after general surgery.
        Anesthesiology. 2012; 116: 658-664
        • Mizota T.
        • Hamada M.
        • Segawa H.
        Relationship between intraoperative hypotension and acute kidney injury after living donor liver transplantation: a retrospective analysis.
        J Cardiothorac Vasc Anesth. 2017; 31: 582-589
        • Schmid S.
        • Kapfer B.
        • Heim M.
        • et al.
        Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial.
        Crit Care. 2016; 20: 1-11
        • Roshanov P.S.
        • Rochwerg B.
        • Patel A.
        • et al.
        Enzyme inhibitors or angiotensin II receptor blockers.
        Anesthesiology. 2017; 126: 16-27
        • Salmasi V.
        • Maheshwari K.
        • Dongsheng Y.
        • et al.
        Thresholds, and acute kidney and myocardial injury after noncardiac surgery a retrospective cohort analysis.
        Anesthesiology. 2017; 126: 47-65
        • Babazade R.
        • Yilmaz H.O.
        • Zimmerman N.M.
        • et al.
        Association between intraoperative low blood pressure and development of surgical site infection after colorectal surgery: a retrospective cohort study.
        Ann Surg. 2016; 6: 1058-1064
        • Hallqvist L.
        • Martensson J.
        • Granath F.
        • Sahlen A.
        • Bell M.
        Intraoperative hypotension is associated with myocardial damage in noncardiac surgery: an observational study.
        Eur J Anaesthesiol. 2016; 33: 450-456
        • van Waes J.A.R.
        • van Klei W.A.
        • Wijeysundera D.N.
        • Van Wolfswinkel L.
        • Lindsay T.F.
        • Beattie W.S.
        Association between intraoperative hypotension and myocardial injury after vascular surgery.
        Anesthesiology. 2016; 124: 35-44
        • Mascha E.J.
        • Yang D.
        • Weiss S.
        • Sessler D.I.
        Intraoperative mean arterial pressure variability and 30-day mortality in patients having noncardiac surgery.
        Anesthesiology. 2015; 123: 79-91
        • Pipanmekaporn T.
        • Punjasawadwong Y.
        • Charuluxananan S.
        • et al.
        Incidence of and risk factors for cardiovascular complications after thoracic surgery for noncancerous lesions.
        J Cardiothorac Vasc Anesth. 2014; 28: 960-965
        • Bijker J.B.
        • van Klei W.A.
        • Vergouwe Y.
        • et al.
        Intraoperative hypotension and 1-year mortality after noncardiac surgery.
        Anesthesiology. 2009; 111: 1217-1226
        • Kheterpal S.
        • O’Reilly M.
        • Englesbe M.J.
        • et al.
        Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery.
        Anesthesiology. 2009; 110: 58-66
        • White S.M.
        • Moppett I.K.
        • Griffiths R.
        • et al.
        Secondary analysis of outcomes after 11,085 hip fracture operations from the prospective UK Anaesthesia Sprint Audit of Practice (ASAP-2).
        Anaesthesia. 2016; 71: 506-514
        • Brinkman R.
        • HayGlass K.T.
        • Mutch W.A.C.
        • Funk D.J.
        Acute kidney injury in patients undergoing open abdominal aortic aneurysm repair: a pilot observational trial.
        J Cardiothorac Vasc Anesth. 2015; 29: 1212-1219
        • Petsiti A.
        • Tassoudis V.
        • Vretzakis G.
        • et al.
        Depth of anesthesia as a risk factor for perioperative morbidity.
        Anesthesiol Res Pract. 2015; 2015: 829151
        • Marcantonio E.R.
        • Goldman L.
        • Orav E.J.
        • Cook E.F.
        • Thomas H.L.
        • Lee T.H.E.
        The association of intraoperative factors with the development of postoperative delirium.
        Am J Med. 1998; 105: 380-384
        • Tallgren M.
        • Niemi T.
        • Pöyhiä R.
        • et al.
        Acute renal injury and dysfunction following elective abdominal aortic surgery.
        Eur J Vasc Endovasc Surg. 2007; 33: 550-555
        • House L.M.
        • Marolen K.N.
        • St Jacques P.J.
        • McEvoy M.D.
        • Ehrenfeld J.M.
        Surgical Apgar score is associated with myocardial injury after noncardiac surgery.
        J Clin Anesth. 2016; 34: 395-402
        • Sessler D.I.
        • Sigl J.C.
        • Kelley S.D.
        • et al.
        Hospital stay and mortality are increased in patients having a triple low of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia.
        Anesthesiology. 2012; 116: 1195-1203
        • Sabaté S.
        • Mases A.
        • Guilera N.
        • et al.
        Incidence and predictors of major perioperative adverse cardiac and cerebrovascular events in non-cardiac surgery.
        Br J Anaesth. 2011; 107: 879-890
        • Taffé P.
        • Sicard N.
        • Pittet V.
        • Pichard S.
        • Burnand B.
        The occurrence of intra-operative hypotension varies between hospitals: observational analysis of more than 147,000 anaesthesia.
        Acta Anaesthesiol Scand. 2009; 53: 995-1005
        • Sirivatanauksorn Y.
        • Parakonthun T.
        • Premasathian N.
        • et al.
        Renal dysfunction after orthotopic liver transplantation.
        Transplant Proc. 2014; 46: 818-821
        • Tassoudis V.
        • Vretzakis G.
        • Petsiti A.
        • et al.
        Impact of intraoperative hypotension on hospital stay in major abdominal surgery.
        J Anesth. 2011; 25: 492-499
        • Stapelfeldt W.H.
        • Yuan H.
        • Dryden J.K.
        • et al.
        The SLUScore: a novel method for detecting hazardous hypotension in adult patients undergoing noncardiac surgical procedures.
        Anesth Analg. 2017; 124: 1135-1152
        • Jiang X.
        • Chen D.
        • Lou Y.
        • Li Z.
        Risk factors for postoperative delirium after spine surgery in middle- and old-aged patients.
        Aging Clin Exp Res. 2017; 29: 1039-1044
        • Yang L.
        • Sun D.F.
        • Han J.
        • Liu R.
        • Wang L.J.
        • Zhang Z.Z.
        Effects of intraoperative hemodynamics on incidence of postoperative delirium in elderly patients: a retrospective study.
        Med Sci Monit. 2016; 22: 1093-1100
        • Yue J.
        • Luo Z.
        • Guo D.
        • et al.
        Evaluation of acute kidney injury as defined by the risk, injury, failure, loss, and end-stage criteria in critically ill patients undergoing abdominal aortic aneurysm repair.
        Chin Med J (Engl). 2013; 126: 431-436
        • Franck M.
        • Radtke F.M.
        • Prahs C.
        • et al.
        Documented intraoperative hypotension according to the three most common definitions does not match the application of antihypotensive medication.
        J Int Med Res. 2011; 39: 846-856
        • Patti R.
        • Saitta M.
        • Cusumano G.
        • Termine G.
        • Di Vita G.
        Risk factors for postoperative delirium after colorectal surgery for carcinoma.
        Eur J Oncol Nurs. 2011; 15: 519-523
        • Vasivej T.
        • Sathirapanya P.
        • Kongkamol C.
        Incidence and risk factors of perioperative stroke in noncardiac, and nonaortic and its major branches surgery.
        J Stroke Cerebrovasc Dis. 2016; 25: 1172-1176
        • Thakar C.V.
        • Kharat V.
        • Blanck S.
        • Leonard A.C.
        Acute kidney injury after gastric bypass surgery.
        Clin J Am Soc Nephrol. 2007; 2: 426-430
        • Barone J.E.
        • Bull M.B.
        • Cussatti E.H.
        • Miller K.D.
        • Tucker J.B.
        Perioperative myocardial infarction in low-risk patients undergoing noncardiac surgery is associated with Intraoperative hypotension.
        J Intensive Care Med. 2002; 17: 250-255
        • Lima E.Q.
        • Zanetta D.M.T.
        • Castro I.
        • et al.
        Risk factors for development of acute renal failure after liver transplantation.
        Ren Fail. 2003; 25: 553-560
        • Nakamura K.
        • Matsuyama M.
        • Yano M.
        • et al.
        Open surgery or stent repair for descending aortic diseases: results and risk factor analysis.
        Scand Cardiovasc J. 2009; 43: 201-207
        • Davidovic L.B.
        • Maksic M.
        • Koncar I.
        • Ilic N.
        Open repair of AAA in a high volume center.
        World J Surg. 2017; 41: 884-891
        • Sharma S.K.
        • McCauley R.
        • Cottam D.
        • et al.
        Acute changes in renal function after laparoscopic gastric surgery for morbid obesity.
        Surg Obes Relat Dis. 2006; 2: 389-392
        • von Elm E.
        • Altman D.G.
        • Egger M.
        • et al.
        Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
        BMJ. 2007; 335: 806-808
        • Schulz K.F.
        • Altman D.G.
        • Moher D.
        Group C. CONSORT 2010 statement : updated guidelines for reporting parallel group randomised trials.
        BMC Med. 2010; 8: 18
        • Vernooij L.M.
        • van Klei W.A.
        • Machina M.
        • Pasma W.
        • Beattie W.S.
        • Peelen L.M.
        Different methods of modelling intraoperative hypotension and their association with postoperative complications in patients undergoing non-cardiac surgery.
        Br J Anaesth. 2018; 120: 1080-1089
        • Wu X.
        • Jiang Z.
        • Ying J.
        • Han Y.
        • Chen Z.
        Optimal blood pressure decreases acute kidney injury after gastrointestinal surgery in elderly hypertensive patients: a randomized study.
        J Clin Anesth. 2017; 43: 77-83
        • Futier E.
        • Lefrant J.-Y.
        • Guinot P.-G.
        • et al.
        Effect of individualized vs standard blood pressure management strategies on postoperative organ dysfunction among high-risk patients undergoing major surgery a randomized clinical trial.
        JAMA. 2017; 318: 1346-1357
        • McCormick P.J.
        • Levin M.A.
        • Lin H.
        • Sessler D.I.
        • Reich D.L.
        Effectiveness of an electronic alert for hypotension and low bispectral index on 90-day postoperative mortality.
        Anesthesiology. 2017; 126: 1113-1120