Critical Care - Research Publications

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    Peri-OPerative Pain Management, Education & De-escalation (POPPMED), a novel anaesthesiologist-led program, significantly reduces acute and long-term postoperative opioid requirements: a retrospective cohort study.
    Heldreich, C ; Meyer, I ; Dube, E ; Hu, R ; Howard, W ; Holmes, N ; Maroon, N ; Weinberg, L ; Tan, CO (Ovid Technologies (Wolters Kluwer Health), 2022)
    INTRODUCTION: The opioid tolerant patient requiring surgery is highly likely to be discharged on high Oral Morphine Equivalent Daily Dosages (OMEDDs), with concomitant risk of increased morbidity and mortality. OBJECTIVES: We proposed that a single anaesthesiologist-led POPPMED (Peri-Operative Pain Management, Education & De-escalation) service could reduce both short and long-term postoperative patient OMEDDs. METHODS: From April 2017, our anaesthesiologist-led POPPMED service, engaged 102 perioperative patients treated with >50mg preoperative OMEDDs. We utilized behavioural interventions; acute opioid reduction and/ or rotation; and regional, multimodal and ketamine analgesia to achieve lowest possible hospital discharge and long term OMEDDs. RESULTS: Patients' preoperative OMEDDs were [median (IQR): 115mg (114mg)], and were representative of an older [age 62 (15) years], high-risk [89% ASA status 3 or 4] patient population. 46% of patients received an acute opioid rotation; 70% received ketamine infusions; and 44% regional analgesia. OMEDDs on discharge [-25mg (82mg), p=0.003] and at 6-12 months [-55mg (105mg ), p<0.0001] were significantly reduced; 84% and 87% of patients achieved OMEDD reduction on discharge and at 6-12 months. Patients with >90mg preoperative OMEDDs achieved greater reductions [discharge: 71% of patients, -52 mg (118 mg) p<0.0001; 6-12 months: 90% of patients, -90mg (115mg), p<0.0001]. On comparison with a pre-POPPMED surgical cohort, Postoperative Day 1-3 11-point Numerical Rating Scale (NRS-11) area under the curve (AUC) measurements at rest and on movement were not significantly different (largest NRS-11:hours AUC difference [median(IQR)] 22 [13], p= 0.24). Hospital length of stay was variably increased. CONCLUSIONS: POPPMED achieved sustained OMEDD reductions safely in an older, high-risk opioid tolerant population, with analgesia comparable to a non-POPPMED cohort, and surgery specific effects on length of stay.
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    Intraoperative low tidal volume ventilation and the risk of ICD-10 coded delirium and the use for antipsychotic medications
    Karalapillai, D ; Weinberg, L ; Serpa Neto, A ; Peyton, PJ ; Ellard, L ; Hu, R ; Pearce, B ; Tan, C ; Story, D ; O'Donnell, M ; Hamilton, P ; Oughton, C ; Galtieri, J ; Appu, S ; Wilson, A ; Eastwood, G ; Bellomo, R ; Jones, DA (BMC, 2022-05-16)
    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 .
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    Intra-operative ventilator mechanical power as a predictor of postoperative pulmonary complications in surgical patients A secondary analysis of a randomised clinical trial
    Karalapillai, D ; Weinberg, L ; Neto A, S ; Peyton, P ; Ellard, L ; Hu, R ; Pearce, B ; Tan, CO ; Story, D ; O'Donnell, M ; Hamilton, P ; Oughton, C ; Galtieri, J ; Wilson, A ; Eastwood, G ; Bellomo, R ; Jones, DA (LIPPINCOTT WILLIAMS & WILKINS, 2022-01)
    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.
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    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
    Heldreich, C ; Ganatra, S ; Lim, Z ; Meyer, I ; Hu, R ; Weinberg, L ; Tan, CO (BMC, 2022-01-21)
    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.
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    The effects of intravenous lignocaine on depth of anaesthesia and intraoperative haemodynamics during open radical prostatectomy.
    Weinberg, L ; Jang, J ; Rachbuch, C ; Tan, C ; Hu, R ; McNicol, L (Springer Science and Business Media LLC, 2017-07-06)
    BACKGROUND: Lignocaine is a local anaesthetic agent, which is also commonly used as a perioperative analgesic adjunct to accelerate rehabilitation and enhance recovery after surgery. Lignocaine's systemic effects on intraoperative haemodynamics and volatile anaesthetic requirements are not well explored. Therefore, we evaluated the effects of intravenous lignocaine on intraoperative volatile agent requirements and haemodynamics in patients undergoing major abdominal surgery. METHODS: We performed an analysis of 76 participants who underwent elective open radical retropubic prostatectomy. Patients received lignocaine (1.5 mg/kg loading dose) followed by an infusion (1.5 mg/kg/h) for the duration of surgery, or saline at an equivalent rate. The aims of the study were to evaluate the end-tidal sevoflurane concentration required to maintain a bispectral index of between 40 and 60. Measurements included intraoperative blood pressure, heart rate, and the volume of intravenous fluids and dosage of vasoactive medications administered. RESULTS: The average end-tidal sevoflurane concentration was lower in the Lignocaine group compared to saline [1.49% (SD: 0.32) vs. 1.89% (SD: 0.29); 95% CI 0.26-0.5, p < 0.001]. In the Lignocaine group, the average mean arterial pressure was 80.3 mmHg (SD: 4.9) compared to 85.1 mmHg (SD: 5.4) in the Saline group (95% CI 2.4-7.1, p < 0.001). Systolic blood pressure was also lower in the Lignocaine group: 121.7 mmHg (SD: 6.1) vs. 128.0 mmHg (SD: 6.4) in the Saline group; 95% CI 3.5-9.2, p < 0.001, as was the mean heart rate [Lignocaine group: 74.9 beats/min (SD: 1.8) vs. 81.5 beats/min (SD: 1.7) in the Saline group, 95% CI 4.1-9.1, p < 0.001]. Maintenance fluid requirements were higher in the Lignocaine group: 3281.1 mL (SD: 1094.6) vs. 2552.6 mL (SD: 1173.5) in the Saline group, 95% CI 206-1251, p = 0.007. There were no differences in the use of vasoactive drugs. CONCLUSIONS: Intravenous lignocaine reduces volatile anaesthetic requirements and lowers blood pressure and heart rate in patients undergoing open radical prostatectomy.
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    Randomised controlled trial to investigate the relationship between mild hypercapnia and cerebral oxygen saturation in patients undergoing major surgery
    Wong, C ; Churilov, L ; Cowie, D ; Tan, CO ; Hu, R ; Tremewen, D ; Pearce, B ; Pillai, P ; Karalapillai, D ; Bellomo, R ; Weinberg, L (BMJ PUBLISHING GROUP, 2020-02)
    OBJECTIVES: The effects of hypercapnia on regional cerebral oxygen saturation (rSO2) during surgery are unclear. We conducted a randomised controlled trial to investigate the relationship between mild hypercapnia and rSO2. We hypothesised that, compared with targeted normocapnia (TN), targeted mild hypercapnia (TMH) during major surgery would increase rSO2. DESIGN: A prospective, randomised, controlled trial in adult participants undergoing elective major surgery. SETTING: A single tertiary centre in Heidelberg, Victoria, Australia. PARTICIPANTS: 40 participants were randomised to either a TMH or TN group (20 to each). INTERVENTIONS: TMH (partial pressure of carbon dioxide in arterial blood, PaCO2, 45-55 mm Hg) or TN (PaCO2 35-40 mm Hg) was delivered via controlled ventilation throughout surgery. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the absolute difference between the two groups in percentage change in rSO2 from baseline to completion of surgery. Secondary endpoints included intraoperative pH, bicarbonate concentration, base excess, serum potassium concentration, incidence of postoperative delirium and length of stay (LOS) in hospital. RESULTS: The absolute difference between the two groups in percentage change in rSO2 from the baseline to the completion of surgery was 19.0% higher in both hemispheres with TMH (p<0.001). On both sides, the percentage change in rSO2 was greater in the TMH group than the TN group throughout the duration of surgery. The difference between the groups became more noticeable over time. Furthermore, postoperative delirium was higher in the TN group (risk difference 0.3, 95% CI 0.1 to 0.5, p=0.02). LOS was similar between groups (5 days vs 5 days; p=0.99). CONCLUSION: TMH was associated with a stable increase in rSO2 from the baseline, while TN was associated with a decrease in rSO2 in both hemispheres in patients undergoing major surgery. This resulted in a clear separation of percentage change in rSO2 from the baseline between TMH and TN over time. Our findings provide the rationale for larger studies on TMH during surgery. TRIAL REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry (ACTRN12616000320459).
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    Intrathecal morphine is associated with reduction in postoperative opioid requirements and improvement in postoperative analgesia in patients undergoing open liver resection
    Tang, J ; Churilov, L ; Tan, CO ; Hu, R ; Pearce, B ; Cosic, L ; Christophi, C ; Weinberg, L (BMC, 2020-08-19)
    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 .