Low tidal volume ventilation for patients undergoing laparoscopic surgery: a secondary analysis of a randomised clinical trial.

BACKGROUND: We recently reported the results for a large randomized controlled trial of low tidal volume ventilation (LTVV) versus conventional tidal volume (CTVV) during major surgery when positive end expiratory pressure (PEEP) was equal between groups. We found no difference in postoperative pulmonary complications (PPCs) in patients who received LTVV. However, in the subgroup of patients undergoing laparoscopic surgery, LTVV was associated with a numerically lower rate of PPCs after surgery. We aimed to further assess the relationship between LTVV versus CTVV during laparoscopic surgery. METHODS: We conducted a post-hoc analysis of this pre-specified subgroup. All patients received volume-controlled ventilation with an applied PEEP of 5 cmH2O and either LTVV (6 mL/kg predicted body weight [PBW]) or CTVV (10 mL/kg PBW). The primary outcome was the incidence of a composite of PPCs within seven days. RESULTS: Three hundred twenty-eight patients (27.2%) underwent laparoscopic surgeries, with 158 (48.2%) randomised to LTVV. Fifty two of 157 patients (33.1%) assigned to LTVV and 72 of 169 (42.6%) assigned to conventional tidal volume developed PPCs within 7 days (unadjusted absolute difference, - 9.48 [95% CI, - 19.86 to 1.05]; p = 0.076). After adjusting for pre-specified confounders, the LTVV group had a lower incidence of the primary outcome than patients receiving CTVV (adjusted absolute difference, - 10.36 [95% CI, - 20.52 to - 0.20]; p = 0.046). CONCLUSION: In this post-hoc analysis of a large, randomised trial of LTVV we found that during laparoscopic surgeries, LTVV was associated with a significantly reduced PPCs compared to CTVV when PEEP was applied equally between both groups. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry no: 12614000790640.

Body mass index is inversely associated with capillary ketones at the time of colonoscopy: Implications for SGLT2i use.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been associated with diabetic ketoacidosis at the time of colonoscopy. This study aimed to identify factors associated with ketone concentrations in SGLT2i-treated type 2 diabetes compared with non-SGLT2i-treated diabetes, and those with impaired fasting glycaemia (IFG) and normoglycaemia. DESIGN: Cross-sectional, multicentre, observational study June-December 2020 in four Australian tertiary hospitals. PARTICIPANTS: Capillary glucose and ketones were measured in people undergoing colonoscopy: 37 SGLT2i-treated and 105 non-SGLT2i-treated type 2 diabetes, 65 IFG and 151 normoglycaemia. MEASUREMENTS: Body mass index (BMI), age, glucose, fasting duration and where relevant, HbA1c and time since last SGLT2i dose. RESULTS: In SGLT2i-treated diabetes, BMI (ρ = -0.43 [95% confidence interval: -0.67, -0.11]) and duration since last SGLT2i dose (ρ = -0.33 [-0.60, 0.00]) correlated negatively with increasing ketones, but there was no correlation with fasting duration. In non-SGLT2i-treated diabetes, BMI correlated negatively (ρ = -0.24 [-0.42, -0.05]) and fasting duration positively (ρ = 0.26 [0.07, 0.43]) with ketones. In IFG participants, only fasting duration correlated with ketones (ρ = 0.28 [0.03, 0.49]). In normoglycaemic participants, there were negative correlations with BMI (ρ = -0.20 [-0.35, -0.04]) and fasting glucose (ρ = -0.31 [-0.45, -0.15]) and positive correlations with fasting duration (ρ = 0.20 [0.04, 0.35]) and age (ρ = 0.19 [0.03, 0.34]). Multiple regression analysis of the entire cohort showed BMI, age and fasting glucose remained independently associated with ketones, but in SGLT2i-treated participants only BMI remained independently associated. CONCLUSIONS: In SGLT2i-treated diabetes, lower BMI was a novel risk factor for higher ketones precolonoscopy. Pending larger confirmatory studies, extra vigilance for ketoacidosis is warranted in these people.

Health-related quality of life after restrictive versus liberal RBC transfusion for cardiac surgery: Sub-study from a randomized clinical trial.

BACKGROUND: Transfusion Requirements in Cardiac Surgery III (TRICS III), a multi-center randomized controlled trial, demonstrated clinical non-inferiority for restrictive versus liberal RBC transfusion for patients undergoing cardiac surgery. However, it is uncertain if transfusion strategy affects long-term health-related quality of life (HRQOL). STUDY DESIGN AND METHODS: In this planned sub-study of Australian patients in TRICS III, we sought to determine the non-inferiority of restrictive versus liberal transfusion strategy on long-term HRQOL and to describe clinical outcomes 24 months postoperatively. The restrictive strategy involved transfusing RBCs when hemoglobin was <7.5 g/dl; the transfusion triggers in the liberal group were: <9.5 g/L intraoperatively, <9.5 g/L in intensive care, or <8.5 g/dl on the ward. HRQOL assessments were performed using the 36-item short form survey version 2 (SF-36v2). Primary outcome was non-inferiority of summary measures of SF-36v2 at 12 months, (non-inferiority margin: -0.25 effect size; restrictive minus liberal scores). Secondary outcomes included non-inferiority of HRQOL at 18 and 24 months. RESULTS: Six hundred seventeen Australian patients received allocated randomization; HRQOL data were available for 208/311 in restrictive and 217/306 in liberal group. After multiple imputation, non-inferiority of restrictive transfusion at 12 months was not demonstrated for HRQOL, and the estimates were directionally in favor of liberal transfusion. Non-inferiority also could not be concluded at 18 and 24 months. Sensitivity analyses supported these results. There were no differences in quality-adjusted life years or composite clinical outcomes up to 24 months after surgery. DISCUSSION: The non-inferiority of a restrictive compared to a liberal transfusion strategy was not established for long-term HRQOL in this dataset.

Restrictive versus liberal transfusion in patients with diabetes undergoing cardiac surgery: An open-label, randomized, blinded outcome evaluation trial.

AIM: To characterize the association between diabetes and transfusion and clinical outcomes in cardiac surgery, and to evaluate whether restrictive transfusion thresholds are harmful in these patients. MATERIALS AND METHODS: The multinational, open-label, randomized controlled TRICS-III trial assessed a restrictive transfusion strategy (haemoglobin [Hb] transfusion threshold <75 g/L) compared with a liberal strategy (Hb <95 g/L for operating room or intensive care unit; or <85 g/L for ward) in patients undergoing cardiac surgery on cardiopulmonary bypass with a moderate-to-high risk of death (EuroSCORE ≥6). Diabetes status was collected preoperatively. The primary composite outcome was all-cause death, stroke, myocardial infarction, and new-onset renal failure requiring dialysis at 6 months. Secondary outcomes included components of the composite outcome at 6 months, and transfusion and clinical outcomes at 28 days. RESULTS: Of the 5092 patients analysed, 1396 (27.4%) had diabetes (restrictive, n = 679; liberal, n = 717). Patients with diabetes had more cardiovascular disease than patients without diabetes. Neither the presence of diabetes (OR [95% CI] 1.10 [0.93-1.31]) nor the restrictive strategy increased the risk for the primary composite outcome (diabetes OR [95% CI] 1.04 [0.68-1.59] vs. no diabetes OR 1.02 [0.85-1.22]; Pinteraction  = .92). In patients with versus without diabetes, a restrictive transfusion strategy was more effective at reducing red blood cell transfusion (diabetes OR [95% CI] 0.28 [0.21-0.36]; no diabetes OR [95% CI] 0.40 [0.35-0.47]; Pinteraction  = .04). CONCLUSIONS: The presence of diabetes did not modify the effect of a restrictive transfusion strategy on the primary composite outcome, but improved its efficacy on red cell transfusion. Restrictive transfusion triggers are safe and effective in patients with diabetes undergoing cardiac surgery.

Continuous bladder urinary oxygen tension as a new tool to monitor medullary oxygenation in the critically ill.

Acute kidney injury (AKI) is common in the critically ill. Inadequate renal medullary tissue oxygenation has been linked to its pathogenesis. Moreover, renal medullary tissue hypoxia can be detected before biochemical evidence of AKI in large mammalian models of critical illness. This justifies medullary hypoxia as a pathophysiological biomarker for early detection of impending AKI, thereby providing an opportunity to avert its evolution. Evidence from both animal and human studies supports the view that non-invasively measured bladder urinary oxygen tension (PuO2) can provide a reliable estimate of renal medullary tissue oxygen tension (tPO2), which can only be measured invasively. Furthermore, therapies that modify medullary tPO2 produce corresponding changes in bladder PuO2. Clinical studies have shown that bladder PuO2 correlates with cardiac output, and that it increases in response to elevated cardiopulmonary bypass (CPB) flow and mean arterial pressure. Clinical observational studies in patients undergoing cardiac surgery involving CPB have shown that bladder PuO2 has prognostic value for subsequent AKI. Thus, continuous bladder PuO2 holds promise as a new clinical tool for monitoring the adequacy of renal medullary oxygenation, with its implications for the recognition and prevention of medullary hypoxia and thus AKI.

Use of a buprenorphine-based pain management protocol is associated with reduced opioid requirements and pain on swallowing in oral mucositis: a retrospective cohort study.

OBJECTIVE: The aim of this study is to ascertain the analgesic efficacy and total oral morphine equivalent daily dose (OMEDD) effect of a buprenorphine-based analgesic protocol in the treatment of severe Oral Mucositis (OM). DESIGN: This is a retrospective cohort study. SETTING: This study was done in a single Quaternary Referral Centre, Haematology Unit. SUBJECTS: Fifty-four stem cell transplant patients suffering at least grade 3 oral mucositis (OM), 24 prior to [Pr-I] and 30 subsequent to [Po-I] a buprenorphine-based OM analgesic protocol. METHODS: We analysed data from the above subjects with the primary outcome measure of difference in total OMEDDs from all opioid types and administration routes, and secondary outcome measures of area under the curve (AUC) of 11-point Numerical Rating Scale (NRS-11) pain assessments, sedation scores and respiratory rate. RESULTS: Post-protocol patients' total OMEDD requirements were significantly reduced [Pr-I: 1961 (1365)mg; Po-I: 928 (625)mg, p = 0.02], as were total NRS-11:hours AUC on swallowing [Pr-I: 54(24) score-hours; Po-I: 41(18) score-hours, p < 0.001]. There were no significant differences in objective measures of OM severity between groups (Number of Grade 3 or 4 OM severity assessments [mean (SD)] Pr-I: 5 (6.2); Po-I: 7 (5.1) or number of days Neutrophil count 0.0 or 0.1 × 109/L; Pr-I: 13 (5.4); Po-I: 15 (4.7)). 5 Pr-I and 4 Po-I patients required ketamine infusions, with 1 Pr-I patient also requiring IV lignocaine. CONCLUSIONS: Use of Buprenorphine via transdermal, sublingual and intravenous Patient Controlled Analgesia (PCA) delivery as part of an analgesic protocol for severe post stem cell transplant oral mucositis in adult patients appears to significantly reduce opioid requirements and pain on swallowing. Further randomised prospective work is required to confirm these associations.

Complete opioid transition to sublingual Buprenorphine after abdominal surgery is associated with significant reductions in opioid requirements, but not reduction in hospital length of stay: a retrospective cohort study.

BACKGROUND: The use of sublingual buprenorphine (SLBup) for acute pain after major abdominal surgery may offer the potential advantages of unique analgesic properties and more reliable absorption during resolving ileus. We hypothesized that complete opioid transition to SLBup rather than oral oxycodone (OOxy) in the early postoperative period after major abdominal surgery would reduce hospital length of stay, and acute pain and total OMEDD (Oral Morphine Equivalent Daily Dose) requirements in the first 24 h from post-parenteral opioid transition. METHODS: We reviewed 146 patients who had undergone elective and emergency abdominal surgery under our quaternary referral centre's Upper Gastro-Intestinal and Colo-Rectal Surgical Units 6 months before and after the introduction of complete postoperative transition to sublingual buprenorphine, rather than oral oxycodone, in July 2017. Our primary endpoint was 24-hourly post-transition OMEDDs; secondary endpoints were 24-hourly post-transition Mean NRS-11 pain scores on movement (POM) and length of hospital stay (LOS). Univariate analysis and linear multivariate regression analyses were used to quantify effect size and identify surgical, patient & other analgesic factors associated with these outcome measures. RESULTS: Patients transitioning to SLBup had reduced 24-hourly post-transition OMEDD requirements on postoperative day 2 (POD) (26 mg less, p = 0.04) and NRS-11 POM at POD1 (0.7 NRS-11 units less, p = 0.01). When adjusting for patient, surgical and special analgesic factors, SLBup was associated with a similar reduction in OMEDDs (Unstandardised beta-coefficient -26 mg, p = 0.0001), but not NRS-11 POM (p = 0.47) or hospital LOS (p = 0.16). CONCLUSIONS: Our change of practice from use of OOxy to SLBup as primary transition opioid from patient-controlled analgesia delivered full opioid agonists was associated with a clinically significant decrease in 24-hourly post-parenteral opioid transition OMEDDs and improved NRS-11 POM, but without an association with hospital LOS after major abdominal surgery. Further prospective randomized work is required to confirm these observed associations and impact on other important patient-centred outcomes.

Intraoperative low tidal volume ventilation and the risk of ICD-10 coded delirium and the use for antipsychotic medications.

BACKGROUND: Low tidal volume (VT) ventilation and its associated increase in arterial carbon dioxide (PaCO2) may affect postoperative neurologic function. We aimed to test the hypothesis that intraoperative low VT ventilation affect the incidence of postoperative ICD-10 coded delirium and/or the need for antipsychotic medications. METHODS: This is a post-hoc analysis of a large randomized controlled trial evaluating low vs. conventional VT ventilation during major non-cardiothoracic, non-intracranial surgery. The primary outcome was the incidence of ICD-10 delirium and/or the use of antipsychotic medications during hospital stay, and the absolute difference with its 95% confidence interval (CI) was calculated. RESULTS: We studied 1206 patients (median age of 64 [55-72] years, 59.0% males, median ARISCAT of 26 [19-37], and 47.6% of ASA 3). ICD-10 coded delirium and /or antipsychotic medication use was diagnosed in 11.2% with similar incidence between low and conventional VT ventilation (11.1% vs. 11.3%; absolute difference, -0.24 [95%CI, -3.82 to 3.32]; p = 0.894). There was no interaction between allocation group and type of surgery. CONCLUSION: In adult patients undergoing major surgery, low VT ventilation was not associated with increased risk of ICD-10 delirium and/or the use of antipsychotic medications during hospital stay. TRIAL REGISTRATION: ANZCTR Identifier: ACTRN12614000790640 .

The Effects of Targeted Changes in Systemic Blood Flow and Mean Arterial Pressure on Urine Oximetry During Cardiopulmonary Bypass.

OBJECTIVES: Poor medullary oxygenation is implicated in the evolution of acute kidney injury. The authors sought to determine if increasing systemic flow and mean arterial pressure could improve urine oxygen tension (PuO2) measured in the bladder, a surrogate of kidney medullary oxygenation, in patients undergoing on-pump cardiac surgery. DESIGN: Randomized crossover study. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty adult patients undergoing cardiopulmonary bypass (CPB) with expected cross-clamp time of >60 minutes and estimated glomerular filtration rate of >30 mL/min/1.73m2. INTERVENTIONS: Sequential 20-minute periods of 2 interventions: Intervention H ("High") or Intervention N ("Normal"). The order of interventions was determined by randomization. Intervention H: targeted CPB flow 3.0 L/min/m2 and mean arterial pressure (MAP) 80 mmHg. Intervention N: targeted CPB flow 2.4 L/min/m2 and MAP 65 mmHg. MEASUREMENTS AND MAIN RESULTS: PuO2 was measured by an oxygen sensor introduced into the bladder via a urinary catheter. Clear separation was achieved in CPB flow and MAP between intervention periods (p < 0.001 for group-time interaction). PuO2 during Intervention H was higher than during Intervention N (p < 0.001 for group-time interaction). After 17 minutes, PuO2 was statistically higher in Intervention H at each time point. There were no differences in markers of hemolysis between interventions. CONCLUSIONS: PuO2 was higher when systemic flow and MAP were increased during CPB. These findings suggest that PuO2 is responsive to changes in hemodynamics and that higher flow and pressure may improve medullary oxygenation.

Intra-operative ventilator mechanical power as a predictor of postoperative pulmonary complications in surgical patients: A secondary analysis of a randomised clinical trial.

BACKGROUND: Studies in critically ill patients suggest a relationship between mechanical power (an index of the energy delivered by the ventilator, which includes driving pressure, respiratory rate, tidal volume and inspiratory pressure) and complications. OBJECTIVE: We aimed to assess the association between intra-operative mechanical power and postoperative pulmonary complications (PPCs). DESIGN: Post hoc analysis of a large randomised clinical trial. SETTING: University-affiliated academic tertiary hospital in Melbourne, Australia, from February 2015 to February 2019. PATIENTS: Adult patients undergoing major noncardiothoracic, nonintracranial surgery. INTERVENTION: Dynamic mechanical power was calculated using the power equation adjusted by the respiratory system compliance (CRS). Multivariable models were used to assess the independent association between mechanical power and outcomes. MAIN OUTCOME MEASURES: The primary outcome was the incidence of PPCs within the first seven postoperative days. The secondary outcome was the incidence of acute respiratory failure. RESULTS: We studied 1156 patients (median age [IQR]: 64 [55 to 72] years, 59.5% men). Median mechanical power adjusted by CRS was 0.32 [0.22 to 0.51] (J min-1)/(ml cmH2O-1). A higher mechanical power was also independently associated with increased risk of PPCs [odds ratio (OR 1.34, 95% CI, 1.17 to 1.52); P < 0.001) and acute respiratory failure (OR 1.40, 95% CI, 1.21 to 1.61; P < 0.001). CONCLUSION: In patients receiving ventilation during major noncardiothoracic, nonintracranial surgery, exposure to a higher mechanical power was independently associated with an increased risk of PPCs and acute respiratory failure. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry no: 12614000790640.

Application of a Series of Two-Dimensional Transesophageal Echocardiographic (2D TEE) Views Across Multiple Axes Improves the Accuracy of Tricuspid Annular Measurements.

OBJECTIVES: Quantification of the tricuspid annulus (TA) is an important factor in determining the requirement for tricuspid annuloplasty in cardiac surgery. Three-dimensional echocardiography (3DE) has shown that the TA is biplanar with an antero-posterior longaxis and septo-lateral shortaxis, and that the commonly used 2D TEE (two-dimensional transesophageal echocardiography) four-chamber view (4ChV) underestimates the true TA longaxis. The authors hypothesized that the use of multiple 2D TEE TA views could attain greater TA long-axis measurements and smaller TA short-axis measurements than the 4ChV, and that the 4ChV has a significant but inconsistent bias relative to the maximal TA diameter measured by these views. DESIGN: Prospective observational study. SETTING: Adult tertiary teaching hospital. PARTICIPANTS: 45 adult patients. INTERVENTIONS: Multiplanar 2D TEE assessment of the tricuspid annulus. MEASUREMENTS AND MAIN RESULTS: Multiplanar assessment reliably produced larger TA long-axis measurements (93% of patients, 95% confidence interval: 81-98%) of (mean [95% confidence interval]) 40 mm (28-50 mm) compared with the 4ChV (34mm [25-44 mm], p < 0.0001) and smaller TA short-axis measurements (29 mm [20-38 mm], p < 0.0001) compared with the 4ChV. TA diameter by 4ChV assessment yielded an average bias of -5.6 mm, with 95% limits of agreement -15 to +3.9 mm compared with the largest TA long-axis measurement by multiplanar assessment. CONCLUSIONS: Multiplanar 2D TEE assessment of the TA long- and short-axis consistently achieves larger and smaller measurements, respectively, than the 4ChV. The 4ChV also is not a reliable index of the TA longaxis. If the time, proficiency, or equipment required for 3DE TA assessment are unavailable, the use of multiple standard and non-standard 2D TEE TA views may offer an alternative for TA assessment.

Decreased mean perfusion pressure as an independent predictor of acute kidney injury after cardiac surgery.

Acute kidney injury after cardiac surgery (AKICS) is common. Previous studies examining the role that mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) may have on AKICS have not taken into account how baseline central venous pressure (CVP) and mean perfusion pressure (MPP) (i.e. MAP - CVP) can influence its evolution. To assess whether the change in MPP to the kidneys (i.e. delta MPP or DMPP) during CPB compared to baseline is an independent predictor of AKICS. After ethical approval, a retrospective observational study was performed on all patients undergoing CPB between October 2013 and June 2015 at a university-affiliated hospital. Known risk factors for the development of AKICS were recorded, as were the MPP values at baseline and during CPB. From this, statistical modelling was performed to identify predictors of postoperative AKICS. 664 patients were identified. Analysis was performed on 513 patients after exclusion. On logistic regression, significant and independent predictors of AKICS included: d20DMPP (cumulative duration of MPP values during CPB that were 20% below baseline and exceeded three consecutive minutes) (P = 0.010); baseline CVP; age; pre-operative creatinine level; and left ventricular (LV) dysfunction (ejection fraction (EF) < 45%). On alternative modelling, the cumulative number of MPP values during CPB that were 10% below baseline was also independently associated with AKICS (P = 0.003). Modelling without taking into account CVP also supported this association. The duration of differences in perfusion pressure to the kidneys during CPB compared to baseline is an independent predictor of AKICS.

Intrathecal morphine is associated with reduction in postoperative opioid requirements and improvement in postoperative analgesia in patients undergoing open liver resection.

BACKGROUND: Our study aimed to test the hypothesis that the addition of intrathecal morphine (ITM) results in reduced postoperative opioid use and enhanced postoperative analgesia in patients undergoing open liver resection using a standardized enhanced recovery after surgery (ERAS) protocol with multimodal analgesia. METHODS: A retrospective analysis of 216 adult patients undergoing open liver resection between June 2010 and July 2017 at a university teaching hospital was conducted. The primary outcome was the cumulative oral morphine equivalent daily dose (oMEDD) on postoperative day (POD) 1. Secondary outcomes included postoperative pain scores, opioid related complications, and length of hospital stay. We also performed a cost analysis evaluating the economic benefits of ITM. RESULTS: One hundred twenty-five patients received ITM (ITM group) and 91 patients received usual care (UC group). Patient characteristics were similar between the groups. The primary outcome - cumulative oMEDD on POD1 - was significantly reduced in the ITM group. Postoperative pain scores up to 24 h post-surgery were significantly reduced in the ITM group. There was no statistically significant difference in complications or hospital stay between the two study groups. Total hospital costs were significantly higher in the ITM group. CONCLUSION: In patients undergoing open liver resection, ITM in addition to conventional multimodal analgesic strategies reduced postoperative opioid requirements and improved analgesia for 24 h after surgery, without any statistically significant differences in opioid-related complications, and length of hospital stay. Hospital costs were significantly higher in patients receiving ITM, reflective of a longer mandatory stay in intensive care. TRIAL REGISTRATION: Registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) under ACTRN12620000001998 .

Effect of Intraoperative Low Tidal Volume vs Conventional Tidal Volume on Postoperative Pulmonary Complications in Patients Undergoing Major Surgery: A Randomized Clinical Trial.

Importance: In patients who undergo mechanical ventilation during surgery, the ideal tidal volume is unclear. Objective: To determine whether low-tidal-volume ventilation compared with conventional ventilation during major surgery decreases postoperative pulmonary complications. Design, Setting, and Participants: Single-center, assessor-blinded, randomized clinical trial of 1236 patients older than 40 years undergoing major noncardiothoracic, nonintracranial surgery under general anesthesia lasting more than 2 hours in a tertiary hospital in Melbourne, Australia, from February 2015 to February 2019. The last date of follow-up was February 17, 2019. Interventions: Patients were randomized to receive a tidal volume of 6 mL/kg predicted body weight (n = 614; low tidal volume group) or a tidal volume of 10 mL/kg predicted body weight (n = 592; conventional tidal volume group). All patients received positive end-expiratory pressure (PEEP) at 5 cm H2O. Main Outcomes and Measures: The primary outcome was a composite of postoperative pulmonary complications within the first 7 postoperative days, including pneumonia, bronchospasm, atelectasis, pulmonary congestion, respiratory failure, pleural effusion, pneumothorax, or unplanned requirement for postoperative invasive or noninvasive ventilation. Secondary outcomes were postoperative pulmonary complications including development of pulmonary embolism, acute respiratory distress syndrome, systemic inflammatory response syndrome, sepsis, acute kidney injury, wound infection (superficial and deep), rate of intraoperative need for vasopressor, incidence of unplanned intensive care unit admission, rate of need for rapid response team call, intensive care unit length of stay, hospital length of stay, and in-hospital mortality. Results: Among 1236 patients who were randomized, 1206 (98.9%) completed the trial (mean age, 63.5 years; 494 [40.9%] women; 681 [56.4%] undergoing abdominal surgery). The primary outcome occurred in 231 of 608 patients (38%) in the low tidal volume group compared with 232 of 590 patients (39%) in the conventional tidal volume group (difference, -1.3% [95% CI, -6.8% to 4.2%]; risk ratio, 0.97 [95% CI, 0.84-1.11]; P = .64). There were no significant differences in any of the secondary outcomes. Conclusions and Relevance: Among adult patients undergoing major surgery, intraoperative ventilation with low tidal volume compared with conventional tidal volume, with PEEP applied equally between groups, did not significantly reduce pulmonary complications within the first 7 postoperative days. Trial Registration: ANZCTR Identifier: ACTRN12614000790640.

30-Day Outcomes Post Veno-Arterial Extra Corporeal Membrane Oxygenation (VA-ECMO) After Cardiac Surgery and Predictors of Survival.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is sometimes needed for post-cardiotomy cardiogenic shock (PCCS). There is little data regarding outcomes in the Australian context, particularly in a non-cardiac transplant centre. Our aim was to report on 30-day outcomes after patients with PCCS treated with VA-ECMO in an Australian non-cardiac transplant tertiary centre, and to determine risk factors for non-survival in this population. METHODS: A retrospective analysis was performed on all adults treated with VA-ECMO for PCCS between August 2001 and September 2016 at our centre. Univariate analysis with adjustment for multiplicity identified risk factors for non-survival. Area under the receiver operating characteristics (AUROC) method was used to assess their predictive value. RESULTS: We identified 64 patients out of 5,502 open-heart surgery cases of which three patients did not meet inclusion criteria. Mean (SD) age was 63 (14) years. Survival to hospital discharge or 30 days post VA-ECMO occurred in 27/61 (44%) patients. VA-ECMO was able to be weaned in 44/61 patients (72%); 54/61 patients (89%) had at least one major complication. Prior to VA-ECMO initiation, no statistically significant differences between survivors and non-survivors could be determined. After VA-ECMO initiation, only 24-hour nadir lactate and 48-hour nadir lactate levels were significantly different between survivors and non-survivors (1.50 mmol/L vs 3.20 mmol/L p=0.001; and 1.20 mmol/L vs. 1.90 mmol/L p=0.001 respectively). For mortality prediction, 24- and 48-hour nadir lactate levels had AUROCs of 0.775 and 0.782, respectively. CONCLUSIONS: VA-ECMO is associated with acceptable survival rates but significant morbidity. Nadir lactate levels in the first 24 and 48 hours after VA-ECMO initiation may be useful in predicting early survival.

Apneic Oxygenation Versus Low-Tidal-Volume Ventilation in Anesthetized Cardiac Surgical Patients: A Prospective, Single-Center, Randomized Controlled Trial.

OBJECTIVES: To compare the physiology of apneic oxygenation with low-tidal-volume (VT) ventilation during harvesting of the left internal mammary artery. DESIGN: Prospective, single-center, randomized trial. SETTING: Single-center teaching hospital. PARTICIPANTS: The study comprised 24 patients who underwent elective coronary artery bypass grafting surgery. INTERVENTIONS: Apneic oxygenation (apneic group: 12 participants) and low-VT ventilation (low-VT group: 12 participants) (2.5 mL/kg ideal body weight) for 15 minutes during harvesting of the left internal mammary artery. MEASUREMENT AND MAIN RESULTS: The primary endpoint was an absolute change in partial pressure of arterial carbon dioxide (PaCO2). Secondary endpoints were changes in arterial pH, pulmonary artery pressures (PAP), cardiac index, and pulmonary artery acceleration time and ease of surgical access. The mean (standard deviation) absolute increase in PaCO2 was 31.8 mmHg (7.6) in the apneic group and 17.6 mmHg (8.2) in the low-VT group (baseline-adjusted difference 14.2 mmHg [95% confidence interval 21.0-7.3], p<0.001). The mean (standard deviation) absolute decrease in pH was 0.15 (0.03) in the apneic group and 0.09 (0.03) in the low-VT group baseline-adjusted difference 0.06 [95% confidence interval 0.03-0.09], p<0.001. Differences in the rate of change over time between groups (time-by-treatment interaction) were observed for PaCO2 (p<0.001), pH (p<0.001), systolic PAP (p = 0.002), diastolic PAP (p = 0.023), and mean PAP (p = 0.034). Both techniques provided adequate ease of surgical access; however, apneic oxygenation was preferred predominantly. CONCLUSIONS: Apneic oxygenation caused a greater degree of hypercarbia and respiratory acidemia compared with low-VT ventilation. Neither technique had deleterious effects on PAP or cardiac function. Both techniques provided adequate ease of surgical access.

Relationship between tricuspid annular excursion and velocity in cardiac surgical patients.

OBJECTIVES: The primary objective of this study was to establish the relationship among tricuspid annular velocity (S'), tricuspid annular plane systolic excursion (TAPSE), and stroke volume (SV) in a cardiac surgical population with and without right ventricular (RV) dysfunction. The secondary objective was to assess the effect of ephedrine on these relationships in a population without RV dysfunction. DESIGN: Prospective, nonrandomized, unblinded study. SETTING: Single tertiary-level, university-affiliated hospital. PARTICIPANTS: Twenty-seven patients undergoing elective coronary artery bypass grafting with no evidence of RV dysfunction (Group 1). Sixteen ventilated postcardiac surgical patients with suspected RV dysfunction (Group 2). INTERVENTIONS: Ten mg of intravenous ephedrine to Group 1 only. MEASUREMENTS AND MAIN RESULTS: Using transthoracic echocardiography, S' and TAPSE were measured using color tissue Doppler applied at the RV base in a 4-chamber view. SV was calculated using thermodilution. Six patients in Group 1 and 6 patients in Group 2 were excluded because of poor imaging or ineligibility. Modest correlation was found between TAPSE and SV in Group 1 (R = 0.50, p<0.001). There was no correlation between TAPSE and SV in Group 2. There was no correlation between S' and SV in both groups. In Group 1, the relationship between TAPSE and S' was curvilinear (R = 0.74 pre-ephedrine, p<0.001; R = 0.64, p = 0.009 post-ephedrine). There was no relationship between TAPSE and S' in Group 2. Ephedrine increased S' and TAPSE. The TAPSE-S' relationship was not significantly altered. CONCLUSIONS: In the presence of RV dysfunction, TAPSE did not correlate with cardiac output. In the absence of RV dysfunction, the relationship between TAPSE and S' described a curvilinear relationship.

Nocturnal respiratory abnormalities among ward-level postoperative patients as detected by the Capnostream 20p monitor: A blinded observational study.

PURPOSE: This prospective observational study aimed to establish the frequency of postoperative nocturnal respiratory abnormalities among patients undergoing major surgery who received ward-level care. These abnormalities may have implications for postoperative pulmonary complications (PPCs). METHODS: Eligible patients underwent blinded noninvasive continuous capnography with pulse oximetry using the Capnostream™ 20p monitor over the first postoperative night. All patients received oxygen supplementation and patient-controlled opioid analgesia. The primary outcome was the number of prolonged apnea events (PAEs), defined as end-tidal carbon dioxide (EtCO2) ≤5 mmHg for 30-120 seconds or EtCO2 ≤5 mmHg for >120 seconds with oxygen saturation (SpO2) <85%. Secondary outcomes were the proportion of recorded time that physiological indices were aberrant, including the apnea index (AI), oxygen desaturation index (ODI), integrated pulmonary index (IPI), and SpO2. Exploratory analysis was conducted to assess the associations between PAEs, PPCs, and pre-defined factors. RESULTS: Among 125 patients who had sufficient data for analysis, a total of 1800 PAEs occurred in 67 (53.4%) patients. The highest quartile accounted for 89.1% of all events. Amongst patients who experienced any PAEs, the median (IQR) number of PAE/patient was four (2-12). As proportions of recorded time (median (IQR)), AI, ODI, and IPI were aberrant for 12.4% (0-43.2%), 19.1% (2.0-57.1%), and 11.5% (3.1-33.3%) respectively. Only age, ARISCAT, and opioid consumption/kg were associated with PPCs. CONCLUSIONS: PAE and aberrant indices were frequently detected on the first postoperative night. However, they did not correlate with PPCs. Future research should investigate the significance of detected aberrations.

Multimodal intrathecal analgesia (MITA) with morphine for reducing postoperative opioid use and acute pain following hepato-pancreato-biliary surgery: A multicenter retrospective study.

INTRODUCTION: The optimal analgesic modality for patients undergoing hepato-pancreato-biliary (HPB) surgery remains unknown. The analgesic effects of a multimodal intrathecal analgesia (MITA) technique of intrathecal morphine (ITM) in combination with clonidine and bupivacaine compared to ITM alone have not been investigated in these patients. METHODS: We performed a multicenter retrospective study of patients undergoing complex HPB surgery who received ITM, bupivacaine, and clonidine (MITA group) or ITM-only (ITM group) as part of their perioperative analgesia strategy. The primary outcome was the unadjusted oral morphine equivalent daily dose (oMEDD) in milligrams on postoperative day 1. After adjusting for age, body mass index, hospital allocation, type of surgery, operation length, and intraoperative opioid use, postoperative oMEDD use was investigated using a bootstrapped quantile regression model. Other prespecified outcomes included postoperative pain scores, opioid-related adverse events, major complications, and length of hospital stay. RESULTS: In total, 118 patients received MITA and 155 patients received ITM-only. The median (IQR) cumulative oMEDD use on postoperative day 1 was 20.5 mg (8.6:31.0) in the MITA group and 52.1 mg (18.0:107.0) in the ITM group (P < 0.001). There was a variation in the magnitude of the difference in oMEDD use between the groups for different quartiles. For the MITA group, on postoperative day 1, patients in the 25th percentile required 14.0 mg less oMEDD (95% CI: -25.9 to -2.2; P = 0.025), patients in the 50th percentile required 27.8 mg less oMEDD (95% CI: -49.7 to -6.0; P = 0.005), and patients in the 75th percentile required 38.7 mg less oMEDD (95% CI: -72.2 to -5.1; P = 0.041) compared to patients in the same percentile of the ITM group. Patients in the MITA group had significantly lower pain scores in the postoperative recovery unit and on postoperative days 1 to 3. The incidence of postoperative respiratory depression was low (<1.5%) and similar between groups. Patients in the MITA group had a significantly higher incidence of postoperative hypotension requiring vasopressor support. However, no significant differences were observed in major postoperative complications, or the length of hospital stay. CONCLUSION: In patients undergoing complex HPB surgery, the use of MITA, consisting of ITM in combination with intrathecal clonidine and bupivacaine, was associated with reduced postoperative opioid use and resulted in superior postoperative analgesia without risk of respiratory depression when compared to patients who received ITM alone. A randomized prospective clinical trial investigating these two intrathecal analgesic techniques is justified.