Targeted temperature control following traumatic brain injury: ESICM/NACCS best practice consensus recommendations.

AIMS AND SCOPE: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. METHODS: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. RESULTS: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0-37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. CONCLUSIONS: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.

Association of preoperative beta-blocker use and cardiac complications after major noncardiac surgery: a prospective cohort study.

INTRODUCTION: Cardiac complications after major noncardiac surgery are common and associated with high morbidity and mortality. How preoperative use of beta-blockers may impact perioperative cardiac complications remains unclear. METHODS: In a multicentre prospective cohort study, preoperative beta-blocker use was ascertained in consecutive patients at elevated cardiovascular risk undergoing major noncardiac surgery. Cardiac complications were prospectively monitored and centrally adjudicated by two independent experts. The primary endpoint was perioperative myocardial infarction or injury attributable to a cardiac cause (cardiac PMI) within the first three postoperative days. The secondary endpoints were major adverse cardiac events (MACE), defined as a composite of myocardial infarction, acute heart failure, life-threatening arrhythmia, and cardiovascular death and all-cause death after 365 days. We used inverse probability of treatment weighting to account for differences between patients receiving beta-blockers and those who did not. RESULTS: A total of 3839/10 272 (37.4%) patients (mean age 74 yr; 44.8% female) received beta-blockers before surgery. Patients on beta-blockers were older, and more likely to be male with established cardiorespiratory and chronic kidney disease. Cardiac PMI occurred in 1077 patients, with a weighted odds ratio of 1.03 (95% confidence interval [CI] 0.94-1.12, P=0.55) for patients on beta-blockers. Within 365 days of surgery, 971/10 272 (9.5%) MACE had occurred, with a weighted hazard ratio of 0.99 (95% CI 0.83-1.18, P=0.90) for patients on beta-blockers. CONCLUSION: Preoperative use of beta-blockers was not associated with decreased cardiac complications including cardiac perioperative myocardial infarction or injury and major adverse cardiac event. Additionally, preoperative use of beta-blockers was not associated with increased all-cause death within 30 and 365 days. CLINICAL TRIAL REGISTRATION: NCT02573532.

The number of comorbidities as an important cofactor to ASA class in predicting postoperative outcome: An international multicentre cohort study.

BACKGROUND: Multimorbidity is a growing burden in our ageing society and is associated with perioperative morbidity and mortality. Despite several modifications to the ASA physical status classification, multimorbidity as such is still not considered. Thus, the aim of this study was to quantify the burden of comorbidities in perioperative patients and to assess, independent of ASA class, its potential influence on perioperative outcome. METHODS: In a subpopulation of the prospective ClassIntra® validation study from eight international centres, type and severity of anaesthesia-relevant comorbidities were additionally extracted from electronic medical records for the current study. Patients from the validation study were of all ages, undergoing any type of in-hospital surgery and were followed up until 30 days postoperatively to assess perioperative outcomes. Primary endpoint was the number of comorbidities across ASA classes. The associated postoperative length of hospital stay (pLOS) and Comprehensive Complication Index (CCI®) were secondary endpoints. On a scale from 0 (no complication) to 100 (death) the CCI® measures the severity of postoperative morbidity as a weighted sum of all postoperative complications. RESULTS: Of 1421 enrolled patients, the mean number of comorbidities significantly increased from 1.5 in ASA I (95% CI, 1.1-1.9) to 10.5 in ASA IV (95% CI, 8.3-12.7) patients. Furthermore, independent of ASA class, postoperative complications measured by the CCI® increased per each comorbidity by 0.81 (95% CI, 0.40-1.23) and so did pLOS (geometric mean ratio, 1.03; 95% CI, 1.01-1.06). CONCLUSIONS: These data quantify the high prevalence of multimorbidity in the surgical population and show that the number of comorbidities is predictive of negative postoperative outcomes, independent of ASA class.

Long-term outcomes of perioperative myocardial infarction/injury after non-cardiac surgery.

AIMS: Perioperative myocardial infarction/injury (PMI) following non-cardiac surgery is a frequent cardiac complication. Better understanding of the underlying aetiologies and outcomes is urgently needed. METHODS AND RESULTS: Aetiologies of PMIs detected within an active surveillance and response programme were centrally adjudicated by two independent physicians based on all information obtained during clinically indicated PMI work-up including cardiac imaging among consecutive high-risk patients undergoing major non-cardiac surgery in a prospective multicentre study. PMI aetiologies were hierarchically classified into 'extra-cardiac' if caused by a primarily extra-cardiac disease such as severe sepsis or pulmonary embolism; and 'cardiac', further subtyped into type 1 myocardial infarction (T1MI), tachyarrhythmia, acute heart failure (AHF), or likely type 2 myocardial infarction (lT2MI). Major adverse cardiac events (MACEs) including acute myocardial infarction, AHF (both only from day 3 to avoid inclusion bias), life-threatening arrhythmia, and cardiovascular death as well as all-cause death were assessed during 1-year follow-up. Among 7754 patients (age 45-98 years, 45% women), PMI occurred in 1016 (13.1%). At least one MACE occurred in 684/7754 patients (8.8%) and 818/7754 patients died (10.5%) within 1 year. Outcomes differed starkly according to aetiology: in patients with extra-cardiac PMI, T1MI, tachyarrhythmia, AHF, and lT2MI 51%, 41%, 57%, 64%, and 25% had MACE, and 38%, 27%, 40%, 49%, and 17% patients died within 1 year, respectively, compared to 7% and 9% in patients without PMI. These associations persisted in multivariable analysis. CONCLUSION: At 1 year, most PMI aetiologies have unacceptably high rates of MACE and all-cause death, highlighting the urgent need for more intensive treatments. STUDY REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02573532.

Discrepancy in Reporting of Perioperative Complications: A Retrospective Observational Study.

OBJECTIVE: To assess the discrepancy between perioperative complications, prospectively recorded during a cohort study versus retrospectively from health records. BACKGROUND: Perioperative adverse events are relevant for patient outcome, but incomplete reporting is common. METHODS: Two physicians independently recorded all intraoperative adverse events according to ClassIntra and all postoperative complications according to the Clavien-Dindo classification based on all available health records. These retrospective assessments were compared with the number and severity of those prospectively assessed in the same patients during their inclusion in 1 center of a prospective multicenter cohort study. RESULTS: Interrater agreement between both physicians for retrospective recording was high [intraclass correlation coefficient: 0.89 (95% CI, 0.86, 0.91) for intraoperative and 0.88 (95% CI, 0.85, 0.90) for postoperative complications]. In 320 patients, the incidence rate was higher retrospectively than prospectively for any intraoperative complication (incidence rate ratio: 1.79; 95% CI, 1.50, 2.13) and for any postoperative complication (incidence rate ratio: 2.21; 95% CI, 1.90, 2.56). In 71 patients, the severity of the most severe intraoperative complication was higher in the retrospective than in the prospective data collection, whereas in 69 the grading was lower. In 106 patients, the severity of the most severe postoperative complication was higher in the retrospective than in the prospective data collection, whereas in 19 the grading was lower. CONCLUSIONS: There is a noticeable discrepancy in the number and severity of reported perioperative complications between these 2 data collection methods. On the basis of the double-blinded assessment of 2 independent raters, our study renders prospective underreporting more likely than retrospective overreporting.

Patient blood management programmes: keeping the ball rolling.

Patient blood management programmes have been endorsed by the World Health Organization and multiple medical societies. It seems important to review the progress and results of patient blood management programmes so necessary modifications or new initiatives can be added to achieve their major goals. In this issue of the British Journal of Anaesthesia, Meybohm and colleagues show that a nationwide patient blood management programme had an impact and was potentially cost-effective in centres that previously utilised large amounts of allogeneic blood transfusions. Before implementing a programme, each institution might need to identify the area(s) of deficiency with respect to established patient blood management methods, which will warrant specific focus in subsequent clinical practice reviews.

Independent External Validation of a Preoperative Prediction Model for Delirium After Cardiac Surgery: A Prospective Observational Cohort Study.

OBJECTIVE: This investigation provided independent external validation of an existing preoperative risk prediction model. DESIGN: A prospective observational cohort study of patients undergoing cardiac surgery covering the period between April 16, 2018 and January 18, 2022. SETTING: Two academic hospitals in Switzerland. PARTICIPANTS: Adult patients (≥60 years of age) who underwent elective cardiac surgery, including coronary artery bypass graft, mitral or aortic valve replacement or repair, and combined procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the incidence of postoperative delirium (POD) in the intensive or intermediate care unit, diagnosed using the Intensive Care Delirium Screening Checklist. The prediction model contained 4 preoperative risk factors to which the following points were assigned: Mini-Mental State Examination (MMSE) score ≤23 received 2 points; MMSE 24-27, Geriatric Depression Scale (GDS) >4, prior stroke and/or transient ischemic attack (TIA), and abnormal serum albumin (≤3.5 or ≥4.5 g/dL) received 1 point each. The missing data were handled using multiple imputation. In total, 348 patients were included in the study. Sixty patients (17.4%) developed POD. For point levels in the prediction model of 0, 1, 2, and ≥3, the cumulative incidence of POD was 12.6%, 22.8%, 25.8%, and 35%, respectively. The validation resulted in a pooled area under the receiver operating characteristics curve of 0.60 (median CI, 0.525-0.679). CONCLUSIONS: The evaluated predictive model for delirium after cardiac surgery in this patient cohort showed only poor discriminative capacity but fair calibration.

Guideline adherence to statin therapy and association with short-term and long-term cardiac complications following noncardiac surgery: A cohort study.

BACKGROUND: Peri-operative complications are common and associated with high morbidity and mortality. Optimising the use of statins might be of important benefit in peri-operative care and reduce morbidity and mortality. OBJECTIVE: To evaluate adherence to current guideline recommendations regarding statin therapy and its association with peri-operative and long-term cardiac complications. DESIGN: Prospective cohort study. SETTING: Multicentre study with enrolment from October 2014 to February 2018. PATIENTS: Eight thousand one hundred and sixteen high-risk inpatients undergoing major noncardiac surgery who were eligible for the institutional peri-operative myocardial injury/infarction (PMI) active surveillance and response program. MAIN OUTCOME MEASURES: Class I indications for statin therapy were derived from the current ESC Clinical Practice Guidelines during the time of enrolment. PMI was prospectively defined as an absolute increase in cTn concentration of the 99th percentile in healthy individuals above the preoperative concentration within the first three postoperative days. Long-term cardiac complications included cardiovascular death and spontaneous myocardial infarction (MI) within 120 days. RESULTS: The mean age was 73.7 years; 45.2% were women. Four thousand two hundred and twenty-seven of 8116 patients (52.1%) had a class I indication for statin therapy. Of these, 2440 of 4227 patients (57.7%) were on statins preoperatively. Adherence to statins was lower in women than in men (46.9 versus 63.9%, P  < 0.001). PMI due to type 1 myocardial infarction/injury (T1MI; n  = 42), or likely type 2 MI (lT2MI; n  = 466) occurred in 508 of 4170 (12.2%) patients. The weighted odds ratio in patients on statin therapy was 1.15 [95% confidence interval (CI) 1.01 to 1.31, P  = 0.036]. During the 120-day follow-up, 192 patients (4.6%) suffered cardiovascular death and spontaneous MI. After multivariable adjustment, preoperative use of statins was associated with reduced risk; weighted hazard ratio 0.59 (95% CI 0.41 to 0.86, P  = 0.006). CONCLUSION: Adherence to guideline-recommended statin therapy was suboptimal, particularly in women. Statin use was associated with an increased risk of PMI due to T1MI and lT2MI but reduced risk of cardiovascular death and spontaneous MI within 120 days. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02573532.

Association between self-reported functional capacity and major adverse cardiac events in patients at elevated risk undergoing noncardiac surgery: a prospective diagnostic cohort study.

BACKGROUND: Perioperative cardiovascular guidelines endorse functional capacity estimation, based on 'cut-off' daily activities for risk assessment and climbing two flights of stairs to approximate 4 metabolic equivalents. We assessed the association between self-reported functional capacity and postoperative cardiac events. METHODS: Consecutive patients at elevated cardiovascular risk undergoing in-patient noncardiac surgery were included in this predefined secondary analysis. Self-reported ability to walk up two flights of stairs was extracted from electronic charts. The primary endpoint was a composite of cardiac death and cardiac events at 30 days. Secondary endpoints included the same composite at 1 yr, all-cause mortality, and myocardial injury. RESULTS: Among the 4560 patients, mean (standard deviation) age 73 (SD 8 yr) yr, classified as American Society of Anesthesiologists physical status ≥3 in 61% (n=2786/4560), the 30-day and 1-yr incidences of major adverse cardiac events were 5.7% (258/4560) and 11.2% (509/4560), respectively. Functional capacity less than two flights of stairs was associated with the 30-day composite endpoint (adjusted hazard ratio 1.63, 95% confidence interval [CI] 1.23-2.15) and all other endpoints. The addition of functional capacity information to the revised cardiac risk index (RCRI) significantly improved risk classification (functional capacity plus RCRI vs RCRI: net reclassification improvement [NRI]Events 6.2 [95% CI 3.6-9.9], NRINonevents19.2 [95% CI 18.1-20.0]). CONCLUSIONS: In patients at high cardiovascular risk undergoing noncardiac surgery, self-reported functional capacity less than two flights of stairs was independently associated with major adverse cardiac events and all-cause mortality at 30 days and 1 yr. The addition of self-reported functional capacity to surgical and clinical risk improved risk classification. CLINICAL TRIAL REGISTRATION: INCT 02573532.

Adherence to the European Society of Cardiology/European Society of Anaesthesiology recommendations on preoperative cardiac testing and association with positive results and cardiac events: a cohort study.

BACKGROUND: European Society of Cardiology/European Society of Anaesthesiology (ESC/ESA) guidelines inform cardiac workup before noncardiac surgery based on an algorithm. Our primary hypotheses were that there would be associations between (i) the groups stratified according to the algorithms and major adverse cardiac events (MACE), and (ii) over- and underuse of cardiac testing and MACE. METHODS: This is a secondary analysis of a multicentre prospective cohort. Major adverse cardiac events were a composite of cardiac death, myocardial infarction, acute heart failure, and life-threatening arrhythmia at 30 days. For each cardiac test, pathological findings were defined a priori. We used multivariable logistic regression to measure associations. RESULTS: We registered 359 MACE at 30 days amongst 6976 patients; classification in a higher-risk group using the ESC/ESA algorithm was associated with 30-day MACE; however, discrimination of the ESC/ESA algorithms for 30-day MACE was modest; area under the curve 0.64 (95% confidence interval: 0.61-0.67). After adjustment for sex, age, and ASA physical status, discrimination was 0.72 (0.70-0.75). Overuse or underuse of cardiac tests were not consistently associated with MACE. There was no independent association between test recommendation class and pathological findings (P=0.14 for stress imaging; P=0.35 for transthoracic echocardiography; P=0.52 for coronary angiography). CONCLUSIONS: Discrimination for MACE using the ESC/ESA guidelines algorithms was limited. Overuse or underuse of cardiac tests was not consistently associated with cardiovascular events. The recommendation class of preoperative cardiac tests did not influence their yield. CLINICAL TRIAL REGISTRATION: NCT02573532.

[Prospective Cohort Study of In-Hospital Patients Undergoing Ophthalmic Surgery for the Validation of ClassIntra: Classification of Intraoperative Adverse Events]. / Prospektive Kohortenstudie bei stationären augenchirurgischen Patienten für die Validierung der ClassIntra-Klassifikation für unerwünschte intraoperative Ereignisse.

BACKGROUND: To the best of our knowledge, there is no validated classification to assess intraoperative adverse events (iAEs) in ophthalmic surgery. ClassIntra is a newly developed classification for surgery- and anaesthesia-related iAEs that has been recently validated in various surgical disciplines, but not in ophthalmic surgery. We aim to assess the validity and practicability of ClassIntra in patients undergoing ophthalmic surgery. METHODS: A consecutive sample of in-hospital patients undergoing any type of ophthalmic surgery was included in this single-centre prospective cohort study. iAEs were classified using ClassIntra, consisting of 5 severity grades according to the symptoms of the patient and the required treatment. All patients were followed for two weeks to record all postoperative adverse events according to Clavien-Dindo. The primary endpoint was the risk-adjusted association between the most severe iAE and the weighted sum of all postoperative adverse events within the two-week follow-up using the Comprehensive Complication Index (CCI). In addition, ophthalmologists and anaesthesiologists were asked to complete an online survey assessing the severity of iAEs for 10 fictitious clinical case scenarios. Reliability was assessed by comparing the clinicians' ratings to the prespecified benchmark rating of the study team. RESULTS: In this study, 100 in-hospital patients with an average age of 64 years (SD 15) were included. The majority of all patients were ASA II (n = 53, 53%) or III (n = 42, 42%). Thirty-two iAEs were recorded in 22 patients (17 grade I, 12 grade II, 3 grade III). Ninety-four postoperative adverse events occurred in 50 patients (44 grade I, 36 grade II, 14 grade IIIa). We found a mean difference in CCI of 2,1 (95% confidence interval [CI] - 2,5 to 6,8) per one unit increase in severity grades of ClassIntra. Fifty ophthalmologists and anaesthesiologists completed the online survey (response rate 54%). The intraclass correlation coefficient was 0,79 (95% CI 0,64 to 0,94). CONCLUSIONS: The application of ClassIntra during daily routine in ophthalmic surgery showed the usefulness and practicability of this classification for the standardised assessment of intraoperative adverse events. Although construct validity could not be demonstrated, the good reliability in the survey's rating underlines the criterion validity of this newly developed classification in ophthalmic surgery.

Influence of mild-moderate hypocapnia on intracranial pressure slow waves activity in TBI.

BACKGROUND: In traumatic brain injury (TBI) the patterns of intracranial pressure (ICP) waveforms may reflect pathological processes that ultimately lead to unfavorable outcome. In particular, ICP slow waves (sw) (0.005-0.05 Hz) magnitude and complexity have been shown to have positive association with favorable outcome. Mild-moderate hypocapnia is currently used for short periods to treat critical elevations in ICP. Our goals were to assess changes in the ICP sw activity occurring following sudden onset of mild-moderate hypocapnia and to examine the relationship between changes in ICP sw activity and other physiological variables during the hypocapnic challenge. METHODS: ICP, arterial blood pressure (ABP), and bilateral middle cerebral artery blood flow velocity (FV), were prospectively collected in 29 adult severe TBI patients requiring ICP monitoring and mechanical ventilation in whom a minute volume ventilation increase (15-20% increase in respiratory minute volume) was performed as part of a clinical CO2-reactivity test. The time series were first treated using FFT filter (pass-band set to 0.005-0.05 Hz). Power spectral density analysis was performed. We calculated the following: mean value, standard deviation, variance and coefficient of variation in the time domain; total power and frequency centroid in the frequency domain; cerebrospinal compliance (Ci) and compensatory reserve index (RAP). RESULTS: Hypocapnia led to a decrease in power and increase in frequency centroid and entropy of slow waves in ICP and FV (not ABP). In a multiple linear regression model, RAP at the baseline was the strongest predictor for the decrease in the power of ICP slow waves (p < 0.001). CONCLUSION: In severe TBI patients, a sudden mild-moderate hypocapnia induces a decrease in mean ICP and FV, but also in slow waves power of both signals. At the same time, it increases their higher frequency content and their morphological complexity. The difference in power of the ICP slow waves between the baseline and the hypocapnia period depends on the baseline cerebrospinal compensatory reserve as measured by RAP.

Hypocapnia after traumatic brain injury: how does it affect the time constant of the cerebral circulation?

The time constant of the cerebral arterial bed ("tau") estimates how fast the blood entering the brain fills the arterial vascular sector. Analogous to an electrical resistor-capacitor circuit, it is expressed as the product of arterial compliance (Ca) and cerebrovascular resistance (CVR). Hypocapnia increases the time constant in healthy volunteers and decreases arterial compliance in head trauma. How the combination of hyocapnia and trauma affects this parameter has yet to be studied. We hypothesized that in TBI patients the intense vasoconstrictive action of hypocapnia would dominate over the decrease in compliance seen after hyperventilation. The predominant vasoconstrictive response would maintain an incoming blood volume in the arterial circulation, thereby lengthening tau. We retrospectively analyzed recordings of intracranial pressure (ICP), arterial blood pressure (ABP), and blood flow velocity (FV) obtained from a cohort of 27 severe TBI patients [(39/30 years (median/IQR), 5 women; admission GCS 6/5 (median/IQR)] studied during a standard clinical CO2 reactivity test. The reactivity test was performed by means of a 50-min increase in ventilation (20% increase in respiratory minute volume). CVR and Ca were estimated from these recordings, and their product calculated to find the time constant. CVR significantly increased [median CVR pre-hypocapnia/during hypocapnia: 1.05/1.35 mmHg/(cm3/s)]. Ca decreased (median Ca pre-hypocapnia/during hypocapnia: 0.130/0.124 arbitrary units) to statistical significance (p = 0.005). The product of these two parameters resulted in a significant prolongation of the time constant (median tau pre-hypocapnia/during hypocapnia: 0.136 s/0.152 s, p ˂ .001). Overall, the increase in CVR dominated over the decrease in compliance, hence tau was longer. We demonstrate a significant increase in the time constant of the cerebral circulation during hypocapnia after severe TBI, and attribute this to an increase in cerebrovascular resistance which outweighs the decrease in cerebral arterial bed compliance.

Perioperative Myocardial Injury After Noncardiac Surgery: Incidence, Mortality, and Characterization.

BACKGROUND: Perioperative myocardial injury (PMI) seems to be a contributor to mortality after noncardiac surgery. Because the vast majority of PMIs are asymptomatic, PMI usually is missed in the absence of systematic screening. METHODS: We performed a prospective diagnostic study enrolling consecutive patients undergoing noncardiac surgery who had a planned postoperative stay of ≥24 hours and were considered at increased cardiovascular risk. All patients received a systematic screening using serial measurements of high-sensitivity cardiac troponin T in clinical routine. PMI was defined as an absolute high-sensitivity cardiac troponin T increase of ≥14 ng/L from preoperative to postoperative measurements. Furthermore, mortality was compared among patients with PMI not fulfilling additional criteria (ischemic symptoms, new ECG changes, or imaging evidence of loss of viable myocardium) required for the diagnosis of spontaneous acute myocardial infarction versus those that did. RESULTS: From 2014 to 2015 we included 2018 consecutive patients undergoing 2546 surgeries. Patients had a median age of 74 years and 42% were women. PMI occurred after 397 of 2546 surgeries (16%; 95% confidence interval, 14%-17%) and was accompanied by typical chest pain in 24 of 397 patients (6%) and any ischemic symptoms in 72 of 397 (18%). Crude 30-day mortality was 8.9% (95% confidence interval [CI], 5.7-12.0) in patients with PMI versus 1.5% (95% CI, 0.9-2.0) in patients without PMI (P<0.001). Multivariable regression analysis showed an adjusted hazard ratio of 2.7 (95% CI, 1.5-4.8) for 30-day mortality. The difference was retained at 1 year with mortality rates of 22.5% (95% CI, 17.6-27.4) versus 9.3% (95% CI, 7.9-10.7). Thirty-day mortality was comparable among patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infarction (280/397, 71%) versus those with at least 1 additional criterion (10.4%; 95% CI, 6.7-15.7, versus 8.7%; 95% CI, 4.2-16.7; P=0.684). CONCLUSIONS: PMI is a common complication after noncardiac surgery and, despite early detection during routine clinical screening, is associated with substantial short- and long-term mortality. Mortality seems comparable in patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infarction versus those patients who do. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02573532.

Vasoactive agents to improve brain perfusion: pathophysiology and clinical utilization.

PURPOSE OF REVIEW: This review highlights the aspects of pathophysiology that make it difficult to predict the effects of any attempt to improve brain perfusion and reviews the options to improve brain perfusion according to the needs of an individual patient, focusing on the choice of a suitable threshold for cerebral perfusion pressure. RECENT FINDINGS: Typically, vasopressors or vasodilators that do not directly influence the cerebral vascular bed are used to improve cerebral perfusion. Positive inotropic substances are rarely used, as the relationship between cardiac output and cerebral blood flow is complex and difficult to measure. Combining perfusion pressure monitoring with monitoring of brain metabolism or oxygenation to adapt cerebral perfusion to the needs of an individual patient has been disappointing. Recently, attempts to individualize perfusion pressure based on measurements of cerebrovascular autoregulation have shown promising results in the management of traumatic brain injury and during cardiac surgery. Currently, only preliminary data are available linking optimized cerebral perfusion to improved outcome. SUMMARY: Optimizing cerebral perfusion remains a difficult goal. All our attempts to manipulate brain perfusion are influenced in an unpredictable manner by underlying diseases. Autoregulation-based strategies to individualize cerebral perfusion management warrant further investigation.

Effect of Mild Hypocapnia on Critical Closing Pressure and Other Mechanoelastic Parameters of the Cerebrospinal System.

OBJECTIVE: Brain arterial critical closing pressure (CrCP) has been studied in several diseases such as traumatic brain injury (TBI), subarachnoid haemorrhage, hydrocephalus, and in various physiological scenarios: intracranial hypertension, decreased cerebral perfusion pressure, hypercapnia, etc. Little or nothing so far has been demonstrated to characterise change in CrCP during mild hypocapnia. METHOD: We retrospectively analysed recordings of intracranial pressure (ICP), arterial blood pressure (ABP) and blood flow velocity from 27 severe TBI patients (mean 39.5 ± 3.4 years, 6 women) in whom a ventilation increase (20% increase in respiratory minute volume) was performed over 50 min as part of a standard clinical CO2 reactivity test. CrCP was calculated using the Windkessel model of cerebral arterial flow. Arteriolar wall tension (WT) was calculated as a difference between CrCP and ICP. The compartmental compliances arterial (C a ) and cerebrospinal fluid space (C i ) were also evaluated. RESULTS: During hypocapnia, ICP decreased from 17±6.8 to 13.2±6.6 mmHg (p < 0.000001). Wall tension increased from 14.5 ± 9.9 to 21.7±9.1 mmHg (p < 0.0002). CrCP, being a sum of WT + ICP, changed significantly from 31.5 ± 11.9 mmHg to 34.9±11.1 mmHg (p < 0.002), and the closing margin (ABP-CrCP) remained constant at an average value of 60 mmHg. C a decreased significantly during hypocapnia by 30% (p < 0.00001) and C i increased by 26% (p < 0.003). CONCLUSION: During hypocapnia in TBI patients, ICP decreases and WT increases. CrCP increases slightly as the rise in wall tension outweighs the decrease in ICP. The closing margin remained unchanged, suggesting that the risk of hypocapnia-induced ischemia might not be increased.

Individualizing Thresholds of Cerebral Perfusion Pressure Using Estimated Limits of Autoregulation.

OBJECTIVES: In severe traumatic brain injury, cerebral perfusion pressure management based on cerebrovascular pressure reactivity index has the potential to provide a personalized treatment target to improve patient outcomes. So far, the methods have focused on identifying "one" autoregulation-guided cerebral perfusion pressure target-called "cerebral perfusion pressure optimal". We investigated whether a cerebral perfusion pressure autoregulation range-which uses a continuous estimation of the "lower" and "upper" cerebral perfusion pressure limits of cerebrovascular pressure autoregulation (assessed with pressure reactivity index)-has prognostic value. DESIGN: Single-center retrospective analysis of prospectively collected data. SETTING: The neurocritical care unit at a tertiary academic medical center. PATIENTS: Data from 729 severe traumatic brain injury patients admitted between 1996 and 2016 were used. Treatment was guided by controlling intracranial pressure and cerebral perfusion pressure according to a local protocol. INTERVENTIONS: None. METHODS AND MAIN RESULTS: Cerebral perfusion pressure-pressure reactivity index curves were fitted automatically using a previously published curve-fitting heuristic from the relationship between pressure reactivity index and cerebral perfusion pressure. The cerebral perfusion pressure values at which this "U-shaped curve" crossed the fixed threshold from intact to impaired pressure reactivity (pressure reactivity index = 0.3) were denoted automatically the "lower" and "upper" cerebral perfusion pressure limits of reactivity, respectively. The percentage of time with cerebral perfusion pressure below (%cerebral perfusion pressure < lower limit of reactivity), above (%cerebral perfusion pressure > upper limit of reactivity), or within these reactivity limits (%cerebral perfusion pressure within limits of reactivity) was calculated for each patient and compared across dichotomized Glasgow Outcome Scores. After adjusting for age, initial Glasgow Coma Scale, and mean intracranial pressure, percentage of time with cerebral perfusion pressure less than lower limit of reactivity was associated with unfavorable outcome (odds ratio %cerebral perfusion pressure < lower limit of reactivity, 1.04; 95% CI, 1.02-1.06; p < 0.001) and mortality (odds ratio, 1.06; 95% CI, 1.04-1.08; p < 0.001). CONCLUSIONS: Individualized autoregulation-guided cerebral perfusion pressure management may be a plausible alternative to fixed cerebral perfusion pressure threshold management in severe traumatic brain injury patients. Prospective randomized research will help define which autoregulation-guided method is beneficial, safe, and most practical.

Prediction of major cardiac events after vascular surgery.

OBJECTIVE: Predicting cardiac events is essential to provide patients with the best medical care and to assess the risk-benefit ratio of surgical procedures. The aim of our study was to evaluate the performance of the Revised Cardiac Risk Index (Lee) and the Vascular Study Group of New England Cardiac Risk Index (VSG) scores for the prediction of major cardiac events in unselected patients undergoing arterial surgery and to determine whether the inclusion of additional risk factors improved their accuracy. METHODS: The study prospectively enrolled 954 consecutive patients undergoing arterial vascular surgery, and the Lee and VSG scores were calculated. Receiver operating characteristic curves for each cardiac risk score were constructed and the areas under the curve (AUCs) compared. Two logistic regression models were done to determine new variables related to the occurrence of major cardiac events (myocardial infarction, heart failure, arrhythmias, and cardiac arrest). RESULTS: Cardiac events occurred in 120 (12.6%) patients. Both scores underestimated the rate of cardiac events across all risk strata. The VSG score had AUC of 0.63 (95% confidence interval [CI], 0.58-0.68), which was higher than the AUC of the Lee score (0.58; 95% CI, 0.52-0.63; P = .03). Addition of preoperative anemia significantly improved the accuracy of the Lee score to an AUC of 0.61 (95% CI, 0.58-0.67; P = .002) but not that of the VSG score. CONCLUSIONS: The Lee and VSG scores have low accuracy and underestimate the risk of major perioperative cardiac events in unselected patients undergoing vascular surgery. The Lee score's accuracy can be increased by adding preoperative anemia. Underestimation of major cardiac complications may lead to incorrect risk-benefit assessments regarding the planned operation.

Associations Between Impaired Cerebral Blood Flow Autoregulation, Cerebral Oxygenation, and Biomarkers of Brain Injury and Postoperative Cognitive Dysfunction in Elderly Patients After Major Noncardiac Surgery.

BACKGROUND: Increasing evidence links postoperative cognitive dysfunction (POCD) to surgery and anesthesia. POCD is recognized as an important neuropsychological adverse outcome in surgical patients, particularly the elderly. This prospective cohort study aimed to investigate whether POCD is associated with impaired intraoperative cerebral autoregulation and oxygenation, and increased levels of biomarkers of brain injury. METHODS: Study subjects were patients ≥65 years of age scheduled for major noncardiac surgery. Cognitive function was assessed before and 1 week after surgery. POCD was diagnosed if a decline of >1 standard deviation of z-scores was present in ≥2 variables of the test battery. The incidence of POCD 1 week after surgery was modeled as a multivariable function of the index of autoregulation (MxA) and tissue oxygenation index (TOI), adjusting for baseline neuropsychological assessment battery (Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery [CERAD-NAB]) total score and the maximum C-reactive protein (CRP) concentration. The biomarkers of brain injury neuron-specific enolase and S100ß protein, age, and level of education were included in secondary multivariable logistic regression analyses. RESULTS: Of the 82 patients who completed the study, 38 (46%) presented with POCD 1 week after surgery. In the multivariable regression analysis, higher intraoperative MxA (odds ratio [OR; 95% confidence interval (CI)], 1.39 [1.01-1.90] for an increase of 0.1 units, P = .08 after Bonferroni adjustment), signifying less effective autoregulation, was not associated with higher odds of POCD. The univariable logistic regression model for MxA yielded an association with POCD (OR [95% CI], 1.44 [1.06-1.95], P = .020). Tissue oxygenation index (1.12 [0.41-3.01] for an increase of 10%, P = 1.0 after Bonferroni adjustment) and baseline CERAD-NAB total score (0.80 [0.45-1.42] for an increase of 10 points, P = .45) did not affect the odds of POCD. POCD was associated with elevated CRP on postoperative day 2 (median [interquartile range]; 175 [81-294] vs 112 [62-142] mg/L, P = .033); however, the maximum CRP value (OR [95% CI], 1.35 [0.97-1.87] for a 2-fold increase, P = .07) had no distinct effect on POCD. CONCLUSIONS: Impairment of intraoperative cerebral blood flow autoregulation is not predictive of early POCD in elderly patients, although secondary analyses indicate that an association probably exists.