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

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.

Intraoperative hypotension and delirium after on-pump cardiac surgery.

BACKGROUND: Delirium is a common complication after cardiac surgery and may be as a result of inadequate cerebral perfusion. We studied delirium after cardiac surgery in relation to intraoperative hypotension (IOH). METHODS: This observational single-centre, cohort study was nested in a randomized trial, on a single intraoperative dose of dexamethasone vs placebo during cardiac surgery. During the first four postoperative days, patients were screened for delirium based on the Confusion Assessment Method (CAM) for Intensive Care Unit on the intensive care unit, CAM on the ward, and by inspection of medical records. To combine depth and duration of IOH, we computed the area under the curve for four blood pressure thresholds. Logistic regression analyses were performed to investigate the association between IOH and the occurrence of postoperative delirium, adjusting for confounding and using a 99% confidence interval to correct for multiple testing. RESULTS: Of the 734 included patients, 99 patients (13%) developed postoperative delirium. The adjusted Odds Ratio for the Mean Arterial Pressure <60 mm Hg threshold was 1.04 (99% confidence interval: 0.99-1.10) for each 1000 mm Hg(2) min(2) AUC(2) increase. IOH, as defined according to the other three definitions, was not associated with postoperative delirium either. Deep and prolonged IOH seemed to increase the risk of delirium, but this was not statistically significant. CONCLUSIONS: Independent of the applied definition, IOH was not associated with the occurrence of delirium after cardiac surgery.

Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma.

The N-methyl-D-aspartate receptor (NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with L-proline in plasma (ß=0.29; P=6.38 × 10(-10)). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with L-proline in CSF (ß=0.28; P=9.68 × 10(-9)). Suggestive evidence of association was found for the D-serine plasma-CSF ratio at the D-amino-acid oxidase (DAO) gene (ß=-0.28; P=9.08 × 10(-8)), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the L-serine to D-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects.

Impact of adding therapeutic recommendations to risk assessments from a prediction model for postoperative nausea and vomiting.

BACKGROUND: In a large cluster-randomized trial on the impact of a prediction model, presenting the calculated risk of postoperative nausea and vomiting (PONV) on-screen (assistive approach) increased the administration of risk-dependent PONV prophylaxis by anaesthetists. This change in therapeutic decision-making did not improve the patient outcome; that is, the incidence of PONV. The present study aimed to quantify the effects of adding a specific therapeutic recommendation to the predicted risk (directive approach) on PONV prophylaxis decision-making and the incidence of PONV. METHODS: A prospective before-after study was conducted in 1483 elective surgical inpatients. The before-period included care-as-usual and the after-period included the directive risk-based (intervention) strategy. Risk-dependent effects on the administered number of prophylactic antiemetics and incidence of PONV were analysed by mixed-effects regression analysis. RESULTS: During the intervention period anaesthetists administered 0.5 [95% confidence intervals (CIs): 0.4-0.6] more antiemetics for patients identified as being at greater risk of PONV. This directive approach led to a reduction in PONV [odds ratio (OR): 0.60, 95% CI: 0.43-0.83], with an even greater reduction in PONV in high-risk patients (OR: 0.45, 95% CI: 0.28-0.72). CONCLUSIONS: Anaesthetists administered more prophylactic antiemetics when a directive approach was used for risk-tailored intervention compared with care-as-usual. In contrast to the previously studied assistive approach, the increase in PONV prophylaxis now resulted in a lower PONV incidence, particularly in high-risk patients. When one aims for a truly 'PONV-free hospital', a more liberal use of prophylactic antiemetics must be accepted and lower-risk thresholds should be set for the actionable recommendations.

Quality of pain treatment after caesarean section: Results of a multicentre cohort study.

BACKGROUND: A large cohort study recently reported high pain scores after caesarean section (CS). The aim of this study was to analyse how pain after CS interferes with patients' activities and to identify possible causes of insufficient pain treatment. METHODS: We analysed pain scores, pain-related interferences (with movement, deep breathing, mood and sleep), analgesic techniques, analgesic consumption, adverse effects and the wish to have received more analgesics during the first 24 h after surgery. To better evaluate the severity of impairment by pain, the results of CS patients were compared with those of patients undergoing hysterectomy. RESULTS: CS patients (n = 811) were compared with patients undergoing abdominal, laparoscopic-assisted vaginal or vaginal hysterectomy (n = 2406, from 54 hospitals). Pain intensity, wish for more analgesics and most interference outcomes were significantly worse after CS compared with hysterectomies. CS patients with spinal or general anaesthesia and without patient-controlled analgesia (PCA) received significantly less opioids on the ward (62% without any opioid) compared with patients with PCA (p < 0.001). Patients with PCA reported pain-related interference with movement and deep breathing between 49% and 52% compared with patients without PCA (between 68% and 73%; p-values between 0.004 and 0.013; not statistically significant after correction for multiple testing). CONCLUSION: In daily clinical practice, pain after CS is much higher than previously thought. Pain management was insufficient compared with patients undergoing hysterectomy. Unfavourable outcome was mainly associated with low opioid administration after CS. Contradictory pain treatment guidelines for patients undergoing CS and for breastfeeding mothers might contribute to reluctance of opioid administration in CS patients.

Internal validation of risk models in clustered data: a comparison of bootstrap schemes.

Internal validity of a risk model can be studied efficiently with bootstrapping to assess possible optimism in model performance. Assumptions of the regular bootstrap are violated when the development data are clustered. We compared alternative resampling schemes in clustered data for the estimation of optimism in model performance. A simulation study was conducted to compare regular resampling on only the patient level with resampling on only the cluster level and with resampling sequentially on both the cluster and patient levels (2-step approach). Optimism for the concordance index and calibration slope was estimated. Resampling of only patients or only clusters showed accurate estimates of optimism in model performance. The 2-step approach overestimated the optimism in model performance. If the number of centers or intraclass correlation coefficient was high, resampling of clusters showed more accurate estimates than resampling of patients. The 3 bootstrap schemes also were applied to empirical data that were clustered. The results presented in this paper support the use of resampling on only the clusters for estimation of optimism in model performance when data are clustered.

Incidence of intraoperative hypoxemia in children in relation to age.

BACKGROUND: Although respiratory problems are by far the most frequent complications of pediatric anesthesia, there are currently no reliable data on the incidence of perioperative hypoxemia in children. Most studies investigating the incidence of pediatric respiratory complications were based on self-report. METHODS: We studied the incidence of intraoperative hypoxemia as well as that of pulse oximeter artifacts prospectively in 575 pediatric noncardiac surgery patients aged between 0 and 16 years operated in a tertiary pediatric university hospital. Subsequently, the incidence of intraoperative hypoxemia was determined retrospectively in 8277 patients registered in an anesthesia information management system (AIMS) of the same hospital. RESULTS: In the prospective cohort, at least 1 episode of oxygen saturation (Spo2) ≤ 90% for at least 1 minute occurred in 69 of 575 cases (12%; 95% confidence interval [CI], 9%-15%). Furthermore, in 35 of 575 (6%; 95% CI, 4%-8%) cases at least 1 true hypoxemic event was observed. In total, 117 episodes of Spo2 ≤ 90% were observed in the prospective study, of which 3 of 117 could not be specified and 67 of 114 (54%; 95% CI, 42%-65%) episodes were classified as true hypoxemia. False-positive low Spo2 values were mainly caused by dislodgment of the pulse oximeter. In the retrospective analysis, Spo2 ≤ 90% and Spo2 ≤ 80% for at least 1 minute were documented in the AIMS in 18% (95% CI, 17%-19%) and 7.5% (95% CI, 7%-8%) of the cases, respectively; 31 and 10 episodes per 100 cases, respectively. The incidence of hypoxemia increased in younger age groups: Spo2 ≤ 90% for at least 1 minute occurred in 56% (95% CI, 49%-63%) of neonates (170 episodes per 100 cases). CONCLUSIONS: The incidence of intraoperative hypoxemia increased with younger age, with the highest incidence in neonates. Because of the high artifact rate, unvalidated pulse oximeter data in AIMS should be interpreted with caution because only up to 65% of all hypoxemic episodes recorded during pediatric anesthesia were caused by true hypoxia.

Effects of the introduction of the WHO "Surgical Safety Checklist" on in-hospital mortality: a cohort study.

OBJECTIVE: To evaluate the effect of implementation of the WHO's Surgical Safety Checklist on mortality and to determine to what extent the potential effect was related to checklist compliance. BACKGROUND: Marked reductions in postoperative complications after implementation of a surgical checklist have been reported. As compliance to the checklists was reported to be incomplete, it remains unclear whether the benefits obtained were through actual completion of a checklist or from an increase in overall awareness of patient safety issues. METHODS: This retrospective cohort study included 25,513 adult patients undergoing non-day case surgery in a tertiary university hospital. Hospital administrative data and electronic patient records were used to obtain data. In-hospital mortality within 30 days after surgery was the main outcome and effect estimates were adjusted for patient characteristics, surgical specialty and comorbidity. RESULTS: After checklist implementation, crude mortality decreased from 3.13% to 2.85% (P = 0.19). After adjustment for baseline differences, mortality was significantly decreased after checklist implementation (odds ratio [OR] 0.85; 95% CI, 0.73-0.98). This effect was strongly related to checklist compliance: the OR for the association between full checklist completion and outcome was 0.44 (95% CI, 0.28-0.70), compared to 1.09 (95% CI, 0.78-1.52) and 1.16 (95% CI, 0.86-1.56) for partial or noncompliance, respectively. CONCLUSIONS: Implementation of the WHO Surgical Checklist reduced in-hospital 30-day mortality. Although the impact on outcome was smaller than previously reported, the effect depended crucially upon checklist compliance.

Influence of propofol-opioid vs isoflurane-opioid anaesthesia on postoperative troponin release in patients undergoing coronary artery bypass grafting.

BACKGROUND: In experimental and clinical studies, volatile anaesthesia has proven to possess cardioprotective properties. However, no randomized controlled trials on the use of isoflurane during the entire cardiac surgical procedure are available. We therefore compared isoflurane-sufentanil vs propofol-sufentanil anaesthesia in patients undergoing coronary artery bypass grafting. METHODS: One hundred patients were randomly assigned to receive isoflurane-sufentanil (I) (n = 51) or propofol-sufentanil (P) (n = 49) anaesthesia, aimed at the same hypnotic depth. Postoperative concentrations of cardiac troponin I (cTnI) were followed for 72 h. Secondary outcome variables were length of stay (LOS) in the intensive care unit (ICU) and in hospital, and 30 day and 1 yr mortality and morbidity, defined as acute myocardial infarction, arrhythmias, and cardiac dysfunction. Groups were compared by an on-treatment analysis, using linear mixed models for repeated measures. RESULTS: Eighty-four patients completed the protocol (I: 41 vs P: 43). Postoperative cTnI concentrations increased to a maximum of I: 2.72 ng ml(-1) (1.78-5.85) and P: 2.64 ng ml(-1) (1.67-4.83), but did not differ between groups (P=0.11). LOS in the ICU and in hospital was similar [ICU I: 18 (17.0-21.5) vs P: 19 (17.0-22.0) h; hospital I: 9 (6.5-8.0) vs P: 8 (6.0-9.0) days]. Cardiac morbidity and mortality in hospital and 30 days after surgery did not differ between groups. One year after surgery, two patients had died of non-cardiac causes. No between-group differences in cardiac morbidity were found. CONCLUSIONS: In this study, the use of isoflurane-sufentanil in comparison with propofol-sufentanil anaesthesia does not afford additional reduction of postoperative cTnI levels.