Intraoperative Hypotension

Intraoperative mortality is now rare, but death within 30 days of surgery remains surprisingly common. Perioperative myocardial infarction is associated with a remarkably high mortality. There are strong associations between hypotension and myocardial injury, myocardial infarction, renal injury, and death. Perioperative arterial blood pressure management was thus the basis of a Perioperative Quality Initiative consensus-building conference held in London in July 2017. The meeting featured a modified Delphi process in which groups addressed various aspects of perioperative arterial pressure. Three consensus statements on intraoperative blood pressure were established. 1) Intraoperative mean arterial pressures below 60-70 mm Hg are associated with myocardial injury, acute kidney injury, and death. Injury is a function of hypotension severity and duration. 2) For adult non-cardiac surgical patients, there is insufficient evidence to recommend a general upper limit of arterial pressure at which therapy should be initiated, although pressures above 160 mm Hg have been associated with myocardial injury and infarction. 3) During cardiac surgery, intraoperative systolic arterial pressure above 140 mm Hg is associated with increased 30 day mortality. Injury is a function of arterial pressure severity and duration. There is increasing evidence that even brief durations of systolic arterial pressure <100 mm Hg and mean arterial pressure <60-70 mm Hg are harmful during non-cardiac surgery.

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. 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. 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 (&#x2265;10&#xa0;min) to mean arterial pressures <80&#xa0;mm Hg and for shorter durations <70&#xa0;mm Hg. Reported risks increase with increased durations for mean arterial pressures <65-60&#xa0;mm Hg or for any exposure <55-50&#xa0;mm Hg. The reported associations suggest that organ injury might occur when mean arterial pressure decreases <80&#xa0;mm Hg for &#x2265;10&#xa0;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.

The relative contributions of intraoperative and postoperative hypotension to perioperative morbidity remain unclear. We determined the association between hypotension and a composite of 30-day myocardial infarction and death over three periods: (1) intraoperative, (2) remaining day of surgery, and (3) during the initial four postoperative days. This was a substudy of POISE-2, a 10,010-patient factorial-randomized trial of aspirin and clonidine for prevention of myocardial infarction. Clinically important hypotension was defined as systolic blood pressure less than 90 mmHg requiring treatment. Minutes of hypotension was the exposure variable intraoperatively and for the remaining day of surgery, whereas hypotension status was treated as binary variable for postoperative days 1 to 4. We estimated the average relative effect of hypotension across components of the composite using a distinct effect generalized estimating model, adjusting for hypotension during earlier periods. Among 9,765 patients, 42% experienced hypotension, 590 (6.0%) had an infarction, and 116 (1.2%) died within 30 days of surgery. Intraoperatively, the estimated average relative effect across myocardial infarction and mortality was 1.08 (98.3% CI, 1.03, 1.12; P < 0.001) per 10-min increase in hypotension duration. For the remaining day of surgery, the odds ratio was 1.03 (98.3% CI, 1.01, 1.05; P < 0.001) per 10-min increase in hypotension duration. The average relative effect odds ratio was 2.83 (98.3% CI, 1.26, 6.35; P = 0.002) in patients with hypotension during the subsequent four days of hospitalization. Clinically important hypotension-a potentially modifiable exposure-was significantly associated with a composite of myocardial infarction and death during each of three perioperative periods, even after adjustment for previous hypotension.

Intraoperative hypotension is associated with acute kidney injury (AKI). Clinicians thus frequently use vasopressors, such as norepinephrine, to maintain blood pressure. However, vasopressors themselves might promote AKI. We sought to determine whether both intraoperative hypotension and cumulative intraoperative norepinephrine dose are independently associated with postoperative AKI in patients undergoing noncardiac surgery. This was a retrospective cohort analysis of 38 338 adult male and female patients who had noncardiac surgery. The primary outcome was AKI within the first 7 postoperative days. We performed adjusted multivariable logistic regression analysis to determine whether intraoperative hypotension (quantified as area under a mean arterial pressure [MAP] of 65 mm Hg) and cumulative intraoperative norepinephrine dose were independently associated with AKI. The median (25th percentile, 75th percentile) area under a MAP of 65 mm Hg was 0.09 (0.02, 0.22) mm Hg&#x2217;day in patients with AKI and 0.05 (0.01, 0.14) mm Hg&#x2217;day in patients without AKI (P<0.001). The cumulative intraoperative norepinephrine dose was 1.92 (0.00, 13.09) &#x3bc;g kg-1 in patients with AKI and 0.00 (0.00, 0.00) &#x3bc;g kg-1 in patients without AKI (P<0.001). Both the area under a MAP of 65 mm Hg (odds ratio 1.55 [95% confidence interval 1.17-2.02] per mm Hg&#x2217;day; P=0.002) and the cumulative intraoperative norepinephrine dose (odds ratio 1.02 [95% confidence interval 1.01-1.02] per &#x3bc;g kg-1; P<0.001) were independently associated with AKI. Both intraoperative hypotension and cumulative intraoperative norepinephrine dose were independently associated with postoperative AKI in patients undergoing noncardiac surgery. Pending results of trials testing whether these relationships are causal, it seems prudent to avoid both profound hypotension and high norepinephrine doses in adults undergoing noncardiac surgery.

Intraoperative arterial hypotension is strongly associated with postoperative major adverse cardiovascular events (MACE); however, whether targeting higher intraoperative mean arterial blood pressures (MAPs) may prevent adverse events remains unclear. This study sought to determine whether targeting higher intraoperative MAP lowers the incidence of postoperative MACE. This single-center randomized controlled trial assigned adult patients at cardiovascular risk undergoing major noncardiac surgery to an intraoperative MAP target of&#xa0;&#x2265;60&#xa0;mm&#xa0;Hg (control) or&#xa0;&#x2265;75&#xa0;mm&#xa0;Hg (MAP&#xa0;&#x2265;75). The primary outcome was acute myocardial injury on postoperative days 0-3 and/or 30-day MACE/acute kidney injury (AKI) (acute coronary syndrome, congestive heart failure, coronary revascularization, stroke, AKI, and all-cause mortality). The secondary outcome was 1-year MACE. In total, 458 patients were randomized (intention-to-treat population: 451). The cumulative intraoperative duration with MAP&#xa0;<65&#xa0;mm&#xa0;Hg was significantly shorter in the MAP&#xa0;&#x2265;75 group (median 9&#xa0;minutes [interquartile range: 3 to 24&#xa0;minutes] vs 23&#xa0;minutes [interquartile range: 8-49&#xa0;minutes]; P&#xa0;< 0.001). The primary outcome incidence was 48% for MAP&#xa0;&#x2265;75 and 52% for control (risk difference&#xa0;-4.2%; 95%&#xa0;CI:&#xa0;-13% to&#xa0;+5%), the primary contributor being AKI (incidence 44%). Acute myocardial injury occurred in 15% (MAP&#xa0;&#x2265;75) and 19% (control) of patients. The secondary outcome incidence was 17% for MAP&#xa0;&#x2265;75 and 15% for control (risk difference&#xa0;+2.7; 95%&#xa0;CI:&#xa0;-4% to&#xa0;+9.5%). These findings do not support universally targeting higher intraoperative blood pressures to reduce postoperative complications. Despite a 60% reduction in hypotensive time with MAP&#xa0;<65&#xa0;mm&#xa0;Hg, no significant reductions in&#xa0;acute myocardial injury or 30-day MACE/AKI could be found. (Biomarkers, Blood Pressure, BIS: Risk Stratification/Management of Patients at Cardiac Risk in Major Noncardiac Surgery [BBB]; NCT02533128).

The association between intraoperative cardiovascular changes and perioperative myocardial injury has chiefly focused on hypotension during noncardiac surgery. However, the relative influence of blood pressure and heart rate (HR) remains unclear. We investigated both individual and codependent relationships among intraoperative HR, systolic blood pressure (SBP), and myocardial injury after noncardiac surgery (MINS). Secondary analysis of the Vascular Events in Noncardiac Surgery Cohort Evaluation (VISION) study, a prospective international cohort study of noncardiac surgical patients. Multivariable logistic regression analysis tested for associations between intraoperative HR and/or SBP and MINS, defined by an elevated serum troponin T adjudicated as due to an ischemic etiology, within 30 days after surgery. Predefined thresholds for intraoperative HR and SBP were: maximum HR >100 beats or minimum HR <55 beats per minute (bpm); maximum SBP >160 mm Hg or minimum SBP <100 mm Hg. Secondary outcomes were myocardial infarction and mortality within 30 days after surgery. After excluding missing data, 1197 of 15,109 patients (7.9%) sustained MINS, 454 of 16,031 (2.8%) sustained myocardial infarction, and 315 of 16,061 patients (2.0%) died within 30 days after surgery. Maximum intraoperative HR >100 bpm was associated with MINS (odds ratio [OR], 1.27 [1.07-1.50]; P < .01), myocardial infarction (OR, 1.34 [1.05-1.70]; P = .02), and mortality (OR, 2.65 [2.06-3.41]; P < .01). Minimum SBP <100 mm Hg was associated with MINS (OR, 1.21 [1.05-1.39]; P = .01) and mortality (OR, 1.81 [1.39-2.37]; P < .01), but not myocardial infarction (OR, 1.21 [0.98-1.49]; P = .07). Maximum SBP >160 mm Hg was associated with MINS (OR, 1.16 [1.01-1.34]; P = .04) and myocardial infarction (OR, 1.34 [1.09-1.64]; P = .01) but, paradoxically, reduced mortality (OR, 0.76 [0.58-0.99]; P = .04). Minimum HR <55 bpm was associated with reduced MINS (OR, 0.70 [0.59-0.82]; P < .01), myocardial infarction (OR, 0.75 [0.58-0.97]; P = .03), and mortality (OR, 0.58 [0.41-0.81]; P < .01). Minimum SBP <100 mm Hg with maximum HR >100 bpm was more strongly associated with MINS (OR, 1.42 [1.15-1.76]; P < .01) compared with minimum SBP <100 mm Hg alone (OR, 1.20 [1.03-1.40]; P = .02). Intraoperative tachycardia and hypotension are associated with MINS. Further interventional research targeting HR/blood pressure is needed to define the optimum strategy to reduce MINS.