Compatibility and stability of an admixture of multiple anaesthetic drugs for opioid-free anaesthesia.

The ability to combine and use drugs in a single infusion device may be useful in resource-limited settings. This study examined the chemical stability of an opioid-sparing mixture of ketamine, lidocaine and magnesium sulphate when combined in a single syringe. High-performance liquid chromatography and atomic absorption spectrophotometry were performed on six syringes containing the three-drug mixture. Since most opioid-sparing techniques typically rely on a 24-hour infusion regime, we tested stability at the initial admixing and 24 hours later. Stability was defined as a measured drug concentration within 10% of expected, with the absence of precipitation or pH alterations. Pharmacokinetic simulations were conducted to further show that the achieved plasma drug concentrations were well within an effective analgesic range. All mixed drug concentration measurements were within the required 10% reference limit. No obvious precipitation or interaction occurred, and pH remained stable. Drug stability was maintained for 24 hours. Pharmacokinetic simulations showed that ketamine and lidocaine were within their minimum analgesic effect concentrations. Our results show that this three-drug mixture is chemically stable for up to 24 hours after mixing, with a pharmacokinetic simulation illustrating safe, clinically useful predicted plasma concentrations when using the described admixture.

Prophylactic phenylephrine and fluid co-administration to reduce spinal hypotension during elective caesarean section in a resource-limited setting: a prospective alternating intervention study.

Spinal hypotension is a common and clinically important problem during caesarean section. Current consensus recommendations for resource-rich settings suggest the use of a titrated phenylephrine infusion, in combination with fluid coloading, for prevention of maternal hypotension. In resource-limited settings, where syringe drivers are unavailable, these recommendations advise the addition of 500 µg phenylephrine to the first 1 l of intravenous fluid given after initiation of spinal anaesthesia, with additional vasopressor boluses as required. This prospective, alternating intervention study compared the use of a conventional phenylephrine rescue bolus strategy for prevention of hypotension, defined as systolic arterial pressure < 90 mmHg, with a phenylephrine infusion given according to the consensus recommendation. We studied 300 women having elective caesarean section. There were 77 (51%) women who developed hypotension in the bolus group vs. 55 (37%) in the phenylephrine infusion group (p = 0.011). This represented a 29% reduction in hypotension, with a number needed to treat of 6.8. The six highest systolic arterial pressure readings occurred in the phenylephrine infusion group (range 166-188 mmHg), and there were four instances of bradycardia (heart rate < 50 beats.min-1 ) with preserved systolic arterial pressure in each group. There were no adverse clinical sequelae, and no differences in neonatal Apgar scores in either group. The consensus recommendation for phenylephrine and fluid co-administration in resource-limited settings appears effective in preventing maternal hypotension, but at the cost of sporadic systolic hypertension.

South African Paediatric Surgical Outcomes Study: a 14-day prospective, observational cohort study of paediatric surgical patients.

BACKGROUND: Children comprise a large proportion of the population in sub-Saharan Africa. The burden of paediatric surgical disease exceeds available resources in Africa, potentially increasing morbidity and mortality. There are few prospective paediatric perioperative outcomes studies, especially in low- and middle-income countries (LMICs). METHODS: We conducted a 14-day multicentre, prospective, observational cohort study of paediatric patients (aged <16 yrs) undergoing surgery in 43 government-funded hospitals in South Africa. The primary outcome was the incidence of in-hospital postoperative complications. RESULTS: We recruited 2024 patients at 43 hospitals. The overall incidence of postoperative complications was 9.7% [95% confidence interval (CI): 8.4-11.0]. The most common postoperative complications were infective (7.3%; 95% CI: 6.2-8.4%). In-hospital mortality rate was 1.1% (95% CI: 0.6-1.5), of which nine of the deaths (41%) were in ASA physical status 1 and 2 patients. The preoperative risk factors independently associated with postoperative complications were ASA physcial status, urgency of surgery, severity of surgery, and an infective indication for surgery. CONCLUSIONS: The risk factors, frequency, and type of complications after paediatric surgery differ between LMICs and high-income countries. The in-hospital mortality is 10 times greater than in high-income countries. These findings should be used to develop strategies to improve paediatric surgical outcomes in LMICs, and support the need for larger prospective, observational paediatric surgical outcomes research in LMICs. CLINICAL TRIAL REGISTRATION: NCT03367832.

A prospective observational study testing liquid crystal phase change type thermometer placed on skin against oesophageal/pharyngeal placed thermometers in participants undergoing general anesthesia.

BACKGROUND: Patient outcomes are influenced by intraoperative temperature management. Oesophageal/pharyngeal temperature monitoring is the standard of care at our institute but is not well tolerated in awake patients. Many non-invasive temperature monitors have been studied. Only the TraxIt® Wearable Children's Underarm Thermometer which contains liquid crystals that undergo phase changes according to temperature is available at our institution. We tested these non-invasive monitors against our standard of care which is the oesophageal/pharyngeal temperature monitor. METHODS: We conducted a prospective observational study of 100 patients receiving general anaesthesia for elective surgery. Patients were eligible for inclusion if they were ≥ 18 years old, were planned to have a general anaesthetic > 60 min during which no body cavity (chest or abdomen) would be opened. Patient temperature was measured with an oesophageal/pharyngeal thermistor probe and skin surface temperature monitors placed over the forehead, in the axilla, over the sternum, and behind the ear (over major vessels to the brain). Temperatures were recorded and then analysed using Altman-Bland plots. Pre-determined clinically relevant limits of agreement were set at -/+ 0.5 °C. RESULTS: From the 100 patients we collected 500 data points for each monitor with an average monitoring time of 102 min (30-300 min) across a range of surgical procedures. None of the skin surface temperature monitors achieved the pre-determined limits of agreement and results were impacted by the use of a forced air warmer. CONCLUSION: The TraxIt® Wearable Children's Underarm Thermometers are not suitable for temperature monitoring during general anaesthesia.

Association between preoperative pulse pressure and perioperative myocardial injury: an international observational cohort study of patients undergoing non-cardiac surgery.

BACKGROUND: The management of elevated blood pressure before non-cardiac surgery remains controversial. Pulse pressure is a stronger predictor of cardiovascular morbidity in the general population than systolic blood pressure alone. We hypothesized that preoperative pulse pressure was associated with perioperative myocardial injury. METHODS: This is a secondary analysis of the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) international cohort study. Participants were aged ≥45 yr and undergoing non-cardiac surgery at 12 hospitals in eight countries. The primary outcome was myocardial injury, defined using serum troponin concentration, within 30 days after surgery. The sample was stratified into quintiles by preoperative pulse pressure. Multivariable logistic regression analysis explored associations between pulse pressure and myocardial injury. We accounted for potential confounding by systolic blood pressure and other co-morbidities known to be associated with postoperative cardiovascular complications. RESULTS: One thousand one hundred and ninety-one of 15 057 (7.9%) patients sustained myocardial injury, which was more frequent amongst patients in the highest two preoperative pulse pressure quintiles {63-75 mm Hg, risk ratio (RR) 1.14 [95% confidence interval (CI): 1.01-1.28], P =0.03; >75 mm Hg, RR 1.15 [95% CI: 1.03-1.29], P =0.02}. After adjustment for systolic blood pressure, preoperative pulse pressure remained the dominant predictor of myocardial injury (63-75 mm Hg, RR 1.20 [95% CI: 1.05-1.37], P <0.01; >75 mm Hg, RR 1.25 [95% CI: 1.06-1.48], P <0.01). Systolic blood pressure >160 mm Hg was not associated with myocardial injury in the absence of pulse pressure >62 mm Hg (RR 0.67 [95% CI: 0.30-1.44], P =0.31). CONCLUSIONS: Preoperative pulse pressure >62 mm Hg was associated with myocardial injury, independent of systolic blood pressure. Elevated pulse pressure may be a useful clinical sign to guide strategies to reduce perioperative myocardial injury.

Heart rate variability as a predictor of hypotension following spinal for elective caesarean section: a prospective observational study.

Post-spinal hypotension remains a common and clinically-important problem during caesarean section, and accurate pre-operative prediction of this complication might enhance clinical management. We conducted a prospective, single-centre, observational study of heart rate variability in 102 patients undergoing elective caesarean section in a South African regional hospital. We performed Holter recording for ≥ 5 min in the hour preceding spinal anaesthesia. The low-frequency/high-frequency ratio component of heart rate variability was compared, using a logistic regression model, with baseline heart rate and body mass index (BMI) as a predictor of hypotension (defined as systolic arterial pressure < 90 mmHg) occurring from the time of spinal insertion until 15 min after delivery of the baby. We also assessed clinically relevant cut-point estimations for low-frequency/high-frequency ratio. Low-frequency/high-frequency ratio predicted hypotension (p = 0.046; OR 1.478, 95%CI 1.008-1.014), with an optimal cut-point estimation of 2.0; this threshold predicted hypotension better than previously determined thresholds (p = 0.003; c-statistic 0.645). Baseline heart rate (p = 0.20; OR 1.022, 95%CI 0.988-1.057) and BMI (p = 0.60; OR 1.017, 95%CI 0.954-1.085) did not predict hypotension. Heart rate variability analysis is a potentially useful clinical tool for the prediction of hypotension. Future studies should consider a low-frequency/high-frequency ratio threshold of 2.0 for prospective validation.

Preoperative heart rate and myocardial injury after non-cardiac surgery: results of a predefined secondary analysis of the VISION study.

BACKGROUND: Increased baseline heart rate is associated with cardiovascular risk and all-cause mortality in the general population. We hypothesized that elevated preoperative heart rate increases the risk of myocardial injury after non-cardiac surgery (MINS). METHODS: We performed a secondary analysis of a prospective international cohort study of patients aged ≥45 yr undergoing non-cardiac surgery. Preoperative heart rate was defined as the last measurement before induction of anaesthesia. The sample was divided into deciles by heart rate. Multivariable logistic regression models were used to determine relationships between preoperative heart rate and MINS (determined by serum troponin concentration), myocardial infarction (MI), and death within 30 days of surgery. Separate models were used to test the relationship between these outcomes and predefined binary heart rate thresholds. RESULTS: Patients with missing outcomes or heart rate data were excluded from respective analyses. Of 15 087 patients, 1197 (7.9%) sustained MINS, 454 of 16 007 patients (2.8%) sustained MI, and 315 of 16 037 patients (2.0%) died. The highest heart rate decile (>96 beats min(-1)) was independently associated with MINS {odds ratio (OR) 1.48 [1.23-1.77]; P<0.01}, MI (OR 1.71 [1.34-2.18]; P<0.01), and mortality (OR 3.16 [2.45-4.07]; P<0.01). The lowest decile (<60 beats min(-1)) was independently associated with reduced mortality (OR 0.50 [0.29-0.88]; P=0.02), but not MINS or MI. The predefined binary thresholds were also associated with MINS, but more weakly than the highest heart rate decile. CONCLUSIONS: Preoperative heart rate >96 beats min(-1) is associated with MINS, MI, and mortality after non-cardiac surgery. This association persists after accounting for potential confounding factors. CLINICAL TRIAL REGISTRATION: NCT00512109.

Effects of dexamethasone as a local anaesthetic adjuvant for brachial plexus block: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Brachial plexus nerve blocks (BPBs) have analgesic and opioid sparing benefits for upper extremity surgery. Single-injection techniques are limited by the pharmacological duration and therapeutic index of local anaesthetics (LAs). Continuous catheter techniques, while effective can present management challenges. Off-label use of perineural dexamethasone as an LA adjuvant has been utilized to prolong single-injection techniques. The objectives of this systematic review and meta-analysis are to assess the contemporary literature and quantify the effects of dexamethasone on BPB. METHODS: The authors searched for randomized, placebo-controlled trials that compared BPB performed with LA alone with that performed with LA and perineural dexamethasone. Meta-analysis was performed using a random effects model with subgroup analysis stratified by LA (long vs intermediate). The primary outcome was duration of sensory block or analgesia; the secondary outcomes were motor block duration, opioid consumption, and BPB complications. RESULTS: Nine trials (801 patients) were included with 393 patients receiving dexamethasone (4-10 mg). Dexamethasone prolonged the analgesic duration for long-acting LA from 730 to 1306 min [mean difference 576 min, 95% confidence interval (CI) 522-631] and for intermediate from 168 to 343 min (mean 175, 95% CI 73-277). Motor block was prolonged from 664 to 1102 min (mean 438, 95% CI 89-787). The most recent trial demonstrated equivalent prolongation with perineural or systemic administration of dexamethasone compared with placebo. CONCLUSIONS: Perineural administration of dexamethasone with LA prolongs BPB effects with no observed adverse events. The effects of systemic administration of dexamethasone on BPB must be investigated.

The endothelial glycocalyx: a review of the vascular barrier.

The endothelial glycocalyx is an important part of the vascular barrier. The glycocalyx is intimately linked to the homoeostatic functions of the endothelium. Damage to the glycocalyx precedes vascular pathology. In the first part of this paper, we have reviewed the structure, physiology and pathology of the endothelial glycocalyx, based on a literature search of the past five years. In the second part, we have systematically reviewed interventions to protect or repair the glycocalyx. Glycocalyx damage can be caused by hypervolaemia and hyperglycaemia and can be prevented by maintaining a physiological concentration of plasma protein, particularly albumin. Other interventions have been investigated in animal models: these require clinical research before their introduction into medical practice.

Cardiac biomarkers in the prediction of risk in the non-cardiac surgery setting.

B-Type natriuretic peptides and troponin measurements have potential in predicting risk in patients undergoing non-cardiac surgery. Using the American Heart Association framework for the evaluation of novel biomarkers, we review the current evidence supporting the peri-operative use of these two biomarkers. In patients having major non-cardiac surgery who are risk stratified using clinical risk scores, the measurement of natriuretic peptides and troponin, both before and after surgery, significantly improves risk stratification. However, only pre- and postoperative natriuretic peptide measurement and postoperative troponin measurement have shown clinical utility. It is now important for trials to be conducted to determine whether integrating pre- and postoperative natriuretic peptide and postoperative troponin measurement into clinical practice is able to improve clinical outcomes in patients undergoing non-cardiac surgery.

The efficacy of peri-operative interventions to decrease postoperative delirium in non-cardiac surgery: a systematic review and meta-analysis.

The purpose of this meta-analysis was to determine the efficacy of peri-operative interventions in decreasing the incidence of postoperative delirium. An electronic search of four databases was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to. We included randomised controlled trials of non-cardiac surgery with a peri-operative intervention and that reported postoperative delirium, and identified 29 trials. Meta-analysis revealed that peri-operative geriatric consultation (OR 0.46, 95% CI 0.32-0.67) and lighter anaesthesia (OR 2.66, 95% CI 1.27-5.56) were associated with a decreased incidence of postoperative delirium. For the other interventions, the point estimate suggested possible protection with prophylactic haloperidol (OR 0.62, 95% CI 0.36-1.05), bright light therapy (OR 0.20, 95% CI 0.03-1.19) and general as opposed to regional anaesthesia (OR 0.76, 95% CI 0.47-1.23). This meta-analysis has shown that peri-operative geriatric consultations with multicomponent interventions and lighter anaesthesia are potentially effective in decreasing the incidence of postoperative delirium.

A review of the role of testosterone in the care of the critically ill patient.

Background: Testosterone is an anabolic and androgenic steroid hormone therapeutically used to produce male sex characteristics. It has also been shown to have a modulating effect on proinflammatory biomarkers. Critical illness is characterised by a proinflammatory and catabolic state and is accompanied by altered testosterone production, which may persist into the recovery phase. Testosterone may, therefore be a potential therapeutic option in critical illness. This paper reviews normal testosterone physiology, and the changes seen during critical illness and systematically reviews testosterone therapy during both the acute and chronic phases of critical illness. Contribution of the study: This article explains the pathophysiology of testosterone during critical illness and explores the therapeutic value of testosterone in the management of critically ill patients.

The influence of clinical risk factors on pre-operative B-type natriuretic peptide risk stratification of vascular surgical patients.

The role of the revised cardiac risk index in risk stratification has recently been challenged by studies reporting on the superior predictive ability of pre-operative B-type natriuretic peptides. We found that in 850 vascular surgical patients initially risk stratified using B-type natriuretic peptides, reclassification with the number of revised cardiac risk index risk factors worsened risk stratification (p < 0.05 for > 0, > 2, > 3 and > 4 risk factors, and p = 0.23 for > 1 risk factor). When evaluated with pre-operative B-type natriuretic peptides, none of the revised cardiac risk index risk factors were independent predictors of major adverse cardiac events in vascular patients. The only independent predictor was B-type natriuretic peptide stratification (OR 5.1, 95% CI 1.8-15 for the intermediate class, and OR 25, 95% CI 8.7-70 for the high-risk class). The clinical risk factors in the revised cardiac risk index cannot improve a risk stratification model based on B-type natriuretic peptides.

A critical analysis of Discovery Health's claims-based risk adjustment of mortality rates in South African private sector hospitals.

In 2019, Discovery Health published a risk adjustment model to determine standardised mortality rates across South African private hospital systems, with the aim of contributing towards quality improvement in the private healthcare sector. However, the model suffers from limitations due to its design and its reliance on administrative data. The publication's aim of facilitating transparency is unfortunately undermined by shortcomings in reporting. When designing a risk prediction model, patient-proximate variables with a sound theoretical or proven association with the outcome of interest should be used. The addition of key condition-specific clinical data points at the time of hospital admission will dramatically improve model performance. Performance could be further improved by using summary risk prediction scores such as the EUROSCORE II for coronary artery bypass graft surgery or the GRACE risk score for acute coronary syndrome. In general, model reporting should conform to published reporting standards, and attempts should be made to test model validity by using sensitivity analyses. In particular, the limitations of machine learning prediction models should be understood, and these models should be appropriately developed, evaluated and reported.

Utility of clinical risk predictors for preoperative cardiovascular risk prediction.

Cardiovascular risk prediction using clinical risk factors is integral to both the European and the American algorithms for preoperative cardiac risk assessment and perioperative management for non-cardiac surgery. We have reviewed these risk factors and their ability to guide clinical decision making. We examine their limitations and attempt to identify factors which may improve their performance when used for clinical risk stratification. To improve the performance of the clinical risk factors, it is necessary to create uniformity in the definitions of both cardiovascular outcomes and the clinical risk factors. The risk factors selected should reflect the degree of organ dysfunction rather than a historical diagnosis. Parsimonious model design should be applied, making use of a minimal number of continuous variables rather than creating overfitted models. The inclusion of age in the model may assist partly in controlling for the duration of risk factor exposure. Risk assignment should occur throughout the perioperative period and the risk factors chosen for model inclusion should vary depending on when the assignment occurs (before operation, intraoperatively, or after operation).

Mortality reduction in cardiac anesthesia and intensive care: results of the first International Consensus Conference.

There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first International Consensus Conference on this topic. The consensus was a continuous international internet-based process with a final meeting on 28 June 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons, and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting, and ranking. Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic ß-blockade, early aspirin therapy, the use of pre-operative intra-aortic balloon counterpulsation, and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. This International Consensus Conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic ß-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.

Outcomes in vascular surgical patients with isolated postoperative troponin leak: a meta-analysis.

Although peri-operative myocardial infarction remains a significant cause of morbidity and mortality following vascular surgery, the significance of an isolated troponin leak is uncertain. This is an elevation of troponin below the diagnostic threshold for a peri-operative myocardial infarction, without symptoms or ischaemic electrocardiography changes or echocardiography signs such as new regional wall motion abnormalities. This meta-analysis aimed to determine the early (< 30 days) and intermediate (< 180 days) outcomes of vascular surgical patients with an isolated troponin leak. A full literature search up to December 2010 identified 593 studies, of which nine (consisting of eight distinct patient cohorts) underwent analysis. An isolated troponin leak was strongly predictive of all-cause mortality at 30 days (OR 5.03, 95% CI 2.88-8.79, p < 0.00001). The associated 30-day mortality in patients with no troponin elevation, an isolated troponin leak or peri-operative myocardial infarction was 2.3%, 11.6% and 21.6%, respectively (p = 0.000001). Insufficient data were available to analyse intermediate-term outcomes. An isolated troponin leak following vascular surgery is strongly associated with short-term mortality.

A prospective observational study of preoperative natriuretic peptide testing in adult non-cardiac surgical patients in hospitals in Western Cape Province, South Africa.

BACKGROUND: International guidelines recommend risk stratification to identify high-risk non-cardiac surgical patients. It is also recommended that all patients aged ≥45 years with significant cardiovascular disease should have preoperative natriuretic peptide (NP) testing. Abnormal preoperative B-type NPs have a strong association with postoperative cardiac complications. In South African hospitals, it is not known how many patients with significant cardiovascular disease scheduled for intermediate- to high-risk surgery will have raised NPs. OBJECTIVES: To determine the prevalence of abnormal (raised) NPs in non-cardiac surgical patients with cardiac clinical risk factors. A secondary objective was to develop a model to identify surgical patients who may benefit from preoperative NP screening. METHODS: The inclusion criteria were patients aged ≥45 years presenting for elective, non-obstetric, intermediate- to high-risk non-cardiac surgery with at least one of the following cardiovascular risk factors: a history of ischaemic heart disease or peripheral vascular disease (coronary equivalent); a history of stroke or transient ischaemic attack; a history of congestive cardiac failure; diabetes mellitus currently on an oral hypoglycaemic agent or insulin; and serum creatinine level >175 µmol/L (>2.0 mg/dL). Blood samples for N-terminal-prohormone B-type NP (NT-proBNP) were collected before induction of anaesthesia. The preoperative prognostic threshold for abnormal (raised) NT-proBNP was ≥300 pg/mL. A generalised linear mixed model was used to determine the association between the risk factors and an abnormal NT-proBNP level. RESULTS: Of 172 patients, 63 (37%) had an elevated preoperative NT-proBNP level. The comorbidities independently associated with elevated preoperative NT-proBNP were coronary artery disease or peripheral vascular disease, congestive cardiac failure, and a creatinine level >175 µmol/L CONCLUSIONS: We strongly recommend that non-cardiac surgical patients aged ≥45 years undergoing intermediate- or high-risk noncardiac surgery with a history of coronary artery disease/peripheral vascular disease, congestive cardiac failure or elevated creatinine have preoperative NP testing as part of risk stratification.