Perioperative management of the vulnerable and failing right ventricle.

Under recognition combined with suboptimal management of right ventricular (RV) dysfunction and failure is associated with significant perioperative morbidity and mortality. The contemporary perioperative team must be prepared with an approach for early recognition and prompt treatment. In this review, a consensus-proposed scoring system is described to provide a pragmatic approach for expeditious decision-making for these complex patients with a vulnerable RV. Importantly, this proposed scoring system incorporates the context of the planned surgical intervention. Further, as the operating room (OR) represents a unique environment where patients are susceptible to numerous insults, a practical approach to anesthetic management and monitoring both in the OR and in the intensive care unit is detailed. Lastly, an escalating approach to the management of RV failure and options for mechanical circulatory support is provided.

Oliceridine, a G protein-selective ligand at the µ-opioid receptor, for the management of moderate to severe acute pain.

Oliceridine is a next-generation investigational intravenous opioid that is a G protein-selective agonist at the µ-opioid receptor. The G protein selectivity of this compound results in potent analgesia with substantially reduced recruitment of ß-arrestin, a signaling pathway associated with opioid-related adverse events. In randomized, placebo- and active-controlled clinical studies, use of oliceridine for the management of moderate to severe acute pain provided potent analgesic effect superior to that observed with placebo, with lower incidence of adverse events, including respiratory events and gastrointestinal events of nausea and vomiting, compared with morphine. Here, we provide a review of the preclinical and clinical data of intravenous oliceridine, a selective agonist, which has the potential to offer a wider therapeutic window than conventional opioids.

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort.

BACKGROUND: Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality. CONCLUSIONS: As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery.

Current concepts of fluid management in enhanced recovery pathways.

Perioperative fluid management impacts outcomes and plays a pivotal role in enhanced recovery pathways (ERPs). There have been major advances in understanding the effects of fluid therapy and administration during the perioperative period. Improving fluid management during this period leads to a decrease in complications, decrease in length of stay (LOS), and enhanced patient outcomes. It is important to consider preoperative and postoperative fluid management to be just as critical as intraoperative management given multiple associated benefits to the patients. Preoperative hydration with (complex) carbohydrate drinks up until 2 h before surgery is safe and should be encouraged, as this helps improve metabolism, decrease insulin resistance, reduce anxiety, and reduce nausea and vomiting. During the intraoperative period, the goals of fluid management are to maintain euvolemia using an individualized plan for fluid and haemodynamic management, matching the needs for monitoring with patient and surgical risk through goal-directed therapy (GDT). By combining the use of fluids and inotropes, GDT uses measurements and indicators of cardiac output and stroke volume to improve blood flow intraoperatively, and ultimately reduce LOS and complications. In the postoperative period, an early transition to oral hydration helps to enhance the conditions for healing and recovery from surgery. I.V. fluid therapy should be kept at a minimum, and urine output should not be the driving force for fluid administration. The optimization of perioperative fluid management is critical to ERPs as it helps improve pulmonary function, tissue oxygenation, gastrointestinal motility, and wound healing.

Digital innovations and emerging technologies for enhanced recovery programmes.

Enhanced recovery programmes (ERPs) are increasingly used to improve post-surgical recovery. However, compliance to various components of ERPs-a key determinant of success-remains sub-optimal. Emerging technologies have the potential to help patients and caregivers to improve compliance with ERPs.Preoperative physical condition, a major determinant of postoperative outcome, could be optimized with the use of text messages (SMS) or digital applications (Apps) designed to facilitate smoking cessation, modify physical activity, and better manage hypertension and diabetes. Several non-invasive haemodynamic monitoring techniques and decision support tools are now available to individualize perioperative fluid management, a key component of ERPs. Objective nociceptive assessment may help to rationalize the use of pain medications, including opioids. Wearable sensors designed to monitor cardio-respiratory function may help in the early detection of clinical deterioration during the postoperative recovery and to address 'failure to rescue'. Activity trackers may be useful to monitor early mobilization, another major element of ERPs. Finally, electronic checklists have been developed to ensure that none of the above-mentioned ERP elements is omitted during the surgical journey.By optimizing compliance to the multiple components of ERPs, digital innovations, non-invasive techniques and wearable sensors have the potential to magnify the clinical and economic benefits of ERPs. Among the growing number of technical innovations, studies are needed to clarify which tools and solutions have real clinical value and are cost-effective.

The effect of anti-emetic doses of dexamethasone on postoperative blood glucose levels in non-diabetic and diabetic patients: a prospective randomised controlled study.

There are few data regarding postoperative hyperglycaemia in non-diabetic compared with diabetic patients following postoperative nausea and vomiting prophylaxis with dexamethasone. Eighty-five non-diabetic patients and patients with type-2 diabetes were randomly allocated to receive intravenous dexamethasone (8 mg) or ondansetron (4 mg). Blood glucose levels were measured at baseline and then 2, 4 and 24 h following induction of anaesthesia. In non-diabetic patients, the mean (SD) maximum blood glucose was higher in those who received dexamethasone compared with ondansetron (9.1 (2.2) mmol.l(-1) vs. 7.8 (1.4) mmol.l(-1) , p = 0.04). In diabetic patients, the mean (SD) maximum blood glucose was also higher in those who received dexamethasone compared with ondansetron (14.0 (2.5) mmol.l(-1) vs. 10.7 (2.4) mmol.l(-1) , p < 0.01). Multivariate analysis demonstrated that dexamethasone administration was a significant predictor of maximum postoperative blood glucose increase (p < 0.01) after adjusting for potential confounders. There was no interaction between baseline blood glucose level, or presence or absence of diabetes, and dexamethasone administration. We conclude that dexamethasone increases postoperative blood glucose levels in both non-diabetics and diabetics.

Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia practice.

BACKGROUND: The present interdisciplinary consensus review proposes clinical considerations and recommendations for anaesthetic practice in patients undergoing gastrointestinal surgery with an Enhanced Recovery after Surgery (ERAS) programme. METHODS: Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials and large prospective cohort studies. For each item of the perioperative treatment pathway, available English-language literature was examined and reviewed. The group reached a consensus recommendation after critical appraisal of the literature. RESULTS: This consensus statement demonstrates that anaesthesiologists control several preoperative, intraoperative and postoperative ERAS elements. Further research is needed to verify the strength of these recommendations. CONCLUSIONS: Based on the evidence available for each element of perioperative care pathways, the Enhanced Recovery After Surgery (ERAS®) Society presents a comprehensive consensus review, clinical considerations and recommendations for anaesthesia care in patients undergoing gastrointestinal surgery within an ERAS programme. This unified protocol facilitates involvement of anaesthesiologists in the implementation of the ERAS programmes and allows for comparison between centres and it eventually might facilitate the design of multi-institutional prospective and adequately powered randomized trials.

Peri-operative fluid management to enhance recovery.

'Enhanced recovery after surgery' protocols implement a series of peri-operative interventions intended to improve recovery after major operations, one aspect of which is fluid management. The pre-operative goal is to prepare a hydrated, euvolaemic patient by avoiding routine mechanical bowel preparation and by encouraging patients to drink clear liquids up to two hours before induction of anaesthesia. The intra-operative goal is to achieve a 'zero' fluid balance at the end of uncomplicated surgery: goal-directed fluid therapy is recommended for poorly prepared or sick patients or those undergoing more complex surgery. The postoperative goal is eating and drinking without intravenous fluid infusions. Postoperative oliguria should be expected and accepted, as urine output does not indicate overall fluid status.

Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 1: pathophysiological considerations.

BACKGROUND: The present article has been written to convey concepts of anaesthetic care within the context of an Enhanced Recovery After Surgery (ERAS) programme, thus aligning the practice of anaesthesia with the care delivered by the surgical team before, during and after surgery. METHODS: The physiological principles supporting the implementation of the ERAS programmes in patients undergoing major abdominal procedures are reviewed using an updated literature search and discussed by a multidisciplinary group composed of anaesthesiologists and surgeons with the aim to improve perioperative care. RESULTS: The pathophysiology of some key perioperative elements disturbing the homoeostatic mechanisms such as insulin resistance, ileus and pain is here discussed. CONCLUSIONS: Evidence-based strategies aimed at controlling the disruption of homoeostasis need to be evaluated in the context of ERAS programmes. Anaesthesiologists could, therefore, play a crucial role in facilitating the recovery process.

Vascular content, tone, integrity, and haemodynamics for guiding fluid therapy: a conceptual approach.

BACKGROUND: Despite many clinical trials and investigative efforts to determine appropriate therapeutic intervention(s) for shock, this topic remains controversial. The use of i.v. fluid has represented the cornerstone for the treatment of hypoperfusion for two centuries. METHODS: As a part of International Acute Dialysis Quality Initiative XII Fluids Workgroup meeting, we sought to incorporate recent advances in our understanding of vascular biology into a more comprehensive yet accessible approach to the patient with hypoperfusion. In this workgroup, we attempted to develop a framework that incorporates key aspects of the vasculature into a diagnostic approach. RESULTS: The four main components of our proposal involve the assessment of the blood flow (BF), vascular content (vC), the vascular barrier (vB), and vascular tone (vT). Any significant perturbation in any of these domains can lead to hypoperfusion at both the macro- and micro-circulatory level. We have termed the BF, vC, vB, and vT diagnostic approach the vascular component (VC) approach. CONCLUSIONS: The VC approach to hypoperfusion has potential advantages to the current diagnostic system. This approach also has the distinct advantage that it can be used to assess the systemic, regional, and micro-vasculature, thereby harmonizing the approach to clinical vascular diagnostics across these levels. The VC approach will need to be tested prospectively to determine if this system can in fact improve outcomes in patients who suffer from hypoperfusion.

I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) remain significant clinical problems for patients, especially nausea. The D2-antagonist droperidol was popular for prophylaxis until safety concerns limited its use. In early testing, APD421 (amisulpride for i.v. injection), a D2/D3-antagonist, has shown promising antiemetic efficacy at very low doses. We conducted a randomized, double-blind, dose-finding study to investigate APD421 in PONV prophylaxis. METHODS: Adult surgical patients with ≥2 Apfel risk factors for PONV undergoing surgery expected to last ≥1 h and receiving standard inhalation anaesthesia were randomized to receive placebo or one of three doses of APD421 (1, 5, or 20 mg) as a single i.v. administration at anaesthesia induction. The primary endpoint was PONV (vomiting/retching or antiemetic rescue) in the 24 h period after surgery. RESULTS: Two hundred and fifteen patients received study drug, 92% female and 60% with ≥3 risk factors. Groups were well balanced for baseline characteristics and risk factors. The PONV incidence was 37/54 [69%; 90% confidence interval (CI), 57-79%] in the placebo group; 28/58 (48%; 90% CI, 37-60%) with 1 mg APD421 (P=0.048); 20/50 (40%; 90% CI, 28-53%) with 5 mg (P=0.006); and 30/53 (57%; 90% CI, 44-68%) with 20 mg (P>0.1). APD421 at 5 mg also significantly improved vomiting, rescue medication use, and nausea rates. The safety profile of APD421 was similar to that of placebo at all doses, with no significant central nervous system (CNS) or cardiac side-effects. CONCLUSIONS: APD421 given i.v. before surgery is safe and effective at reducing PONV in moderate/high-risk adult surgical patients. The optimal dose tested was 5 mg.

Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis.

BACKGROUND: The analgesic efficacy and adverse effects of a single perioperative dose of dexamethasone are unclear. We performed a systematic review to evaluate the impact of a single i.v. dose of dexamethasone on postoperative pain and explore adverse events associated with this treatment. METHODS: MEDLINE, EMBASE, CINAHL, and the Cochrane Register were searched for randomized, controlled studies that compared dexamethasone vs placebo or an antiemetic in adult patients undergoing general anaesthesia and reported pain outcomes. RESULTS: Forty-five studies involving 5796 patients receiving dexamethasone 1.25-20 mg were included. Patients receiving dexamethasone had lower pain scores at 2 h {mean difference (MD) -0.49 [95% confidence interval (CI): -0.83, -0.15]} and 24 h [MD -0.48 (95% CI: -0.62, -0.35)] after surgery. Dexamethasone-treated patients used less opioids at 2 h [MD -0.87 mg morphine equivalents (95% CI: -1.40 to -0.33)] and 24 h [MD -2.33 mg morphine equivalents (95% CI: -4.39, -0.26)], required less rescue analgesia for intolerable pain [relative risk 0.80 (95% CI: 0.69, 0.93)], had longer time to first dose of analgesic [MD 12.06 min (95% CI: 0.80, 23.32)], and shorter stays in the post-anaesthesia care unit [MD -5.32 min (95% CI: -10.49 to -0.15)]. There was no dose-response with regard to the opioid-sparing effect. There was no increase in infection or delayed wound healing with dexamethasone, but blood glucose levels were higher at 24 h [MD 0.39 mmol litre(-1) (95% CI: 0.04, 0.74)]. CONCLUSIONS: A single i.v. perioperative dose of dexamethasone had small but statistically significant analgesic benefits.

Development and validation of a composite score based on clinically meaningful events for the opioid-related symptom distress scale.

PURPOSE: To develop and validate a composite score based on clinically meaningful events (CMEs) for the opioid-related symptom distress scale (OR-SDS) that would be appropriate for use in postoperative clinical trials. METHODS: Secondary analysis of data from 2 multi-site Phase III randomized clinical safety trials: a general surgery trial (N = 1,050) and a coronary artery bypass graft surgery trial (N = 1,636). Validating measures include daily opioid consumption and physician and patient global evaluations of study medication. We empirically defined CMEs for each symptom, using factor analysis and an area under the receiver-operating characteristic analysis of the severity and frequency items of the OR-SDS. Construct validity was examined by testing hypotheses of relationships between composite CME scores and opioid consumption and physician and patient evaluations of study medication. RESULTS: Hypotheses supporting the construct validity of the CME-based composite score were confirmed. Significant associations were found between higher numbers of CMEs with greater opioid consumption and lower likelihood of a positive evaluation of the study medication. CONCLUSIONS: The OR-SDS CME-based composite score demonstrates evidence of construct validity and appears appropriate for use in evaluating patients' opioid-related side effect burden in future postoperative clinical trials.

Acupuncture and related techniques for postoperative pain: a systematic review of randomized controlled trials.

Postoperative pain management remains a significant challenge for all healthcare providers. The objective of this systematic review was to quantitatively evaluate the efficacy of acupuncture and related techniques as adjunct analgesics for acute postoperative pain management. We searched the databases of Medline (1966-2007), CINAHL, The Cochrane Central Register of Controlled Trials (2006), and Scopus for randomized controlled trials (RCTs) using acupuncture for postoperative pain management. We extracted data about postoperative opioid consumption, postoperative pain intensity, and opioid-related side-effects. Combined data were analysed using a random effects model. Fifteen RCTs comparing acupuncture with sham control in the management of acute postoperative pain were included. Weighted mean difference for cumulative opioid analgesic consumption was -3.14 mg (95% confidence interval, CI: -5.15, -1.14), -8.33 mg (95% CI: -11.06, -5.61), and -9.14 mg (95% CI: -16.07, -2.22) at 8, 24, and 72 h, respectively. Postoperative pain intensity (visual analogue scale, 0-100 mm) was also significantly decreased in the acupuncture group at 8 and 72 h compared with the control group. The acupuncture treatment group was associated with a lower incidence of opioid-related side-effects such as nausea (relative risk, RR: 0.67; 95% CI: 0.53, 0.86), dizziness (RR: 0.65; 95% CI: 0.52, 0.81), sedation (RR: 0.78; 95% CI: 0.61, 0.99), pruritus (RR: 0.75; 95% CI: 0.59, 0.96), and urinary retention (RR: 0.29; 95% CI: 0.12, 0.74). Perioperative acupuncture may be a useful adjunct for acute postoperative pain management.

Algorithms for the prevention of postoperative nausea and vomiting: an efficacy and efficiency simulation.

BACKGROUND AND OBJECTIVE: A number of algorithms for the prevention of postoperative nausea and vomiting have been proposed. Their efficacy and efficiency remains unclear. METHODS: We assumed that four antiemetic interventions were similarly effective and achieved additive effects when combined. We applied published and hypothetical algorithms for the prevention of postoperative nausea and vomiting to patient populations with different baseline risks. As indicators of efficacy and efficiency we computed for each baseline risk and each algorithm the total number of patients receiving prophylaxis, the total number of administered interventions, the cumulative 24 h incidence of postoperative nausea and vomiting, and an Efficiency Index (i.e. the number of administered interventions divided by the achieved absolute risk reduction). This was done for cohorts of 100 patients. RESULTS: Ten algorithms were tested in seven populations with different baseline risks. Algorithms were fixed (> or = 1 intervention given to all patients, independent of baseline risk) or risk-adapted (> or = 1 intervention administered depending on the presumed baseline risk). Risk-adapted algorithms were escalating (the greater the baseline risk, the more interventions are given) or dichotomous (a fixed number of interventions is given to high-risk patients only). With some algorithms, when applied to selected patient populations, the average postoperative nausea and vomiting incidence could be decreased below 15%; however, none produced consistent postoperative nausea and vomiting incidences below 20% across all populations. With all, the number of administered antiemetic interventions was the major factor for improved efficacy. Depending on the baseline risk, some algorithms offered potential towards improved efficiency. CONCLUSIONS: Despite improved knowledge on risk factors and antiemetic strategies, none of the tested algorithms completely prevents postoperative nausea and vomiting and none is universally applicable. Anesthesiologists should try to identify the most useful antiemetic strategy for a specific setting. That strategy may be prophylactic or therapeutic or a combination of both, and it should consider institutional policies and individual baseline risks.

Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery.

BACKGROUND: The neurokinin(1) antagonist aprepitant is effective for prevention of chemotherapy-induced nausea and vomiting. We compared aprepitant with ondansetron for prevention of postoperative nausea and vomiting. METHODS: Nine hundred and twenty-two patients receiving general anaesthesia for major abdominal surgery were assigned to receive a single preoperative dose of oral aprepitant 40 mg, oral aprepitant 125 mg, or i.v. ondansetron 4 mg in a randomized, double-blind trial. Vomiting episodes, use of rescue therapy, and nausea severity (verbal rating scale) were documented for 48 h after surgery. Primary efficacy endpoints were complete response (no vomiting and no use of rescue therapy) 0-24 h after surgery and no vomiting 0-24 h after surgery. The secondary endpoint was no vomiting 0-48 h after surgery. RESULTS: Aprepitant at both doses was non-inferior to ondansetron for complete response 0-24 h after surgery (64% for aprepitant 40 mg, 63% for aprepitant 125 mg, and 55% for ondansetron, lower bound of 1-sided 95% CI > 0.65), superior to ondansetron for no vomiting 0-24 h after surgery (84% for aprepitant 40 mg, 86% for aprepitant 125 mg, and 71% for ondansetron; P < 0.001), and superior for no vomiting 0-48 h after surgery (82% for aprepitant, 40 mg, 85% for aprepitant, 125 mg, and 66% for ondansetron; P < 0.001). The distribution of peak nausea scores was lower in both aprepitant groups vs ondansetron (P < 0.05). CONCLUSIONS: Aprepitant was non-inferior to ondansetron in achieving complete response for 24 h after surgery. Aprepitant was significantly more effective than ondansetron for preventing vomiting at 24 and 48 h after surgery, and in reducing nausea severity in the first 48 h after surgery. Aprepitant was generally well tolerated.