Critical Care - Research Publications
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ItemThe hemodynamic effects of intravenous paracetamol (acetaminophen) in patients with chronic liver disease undergoing liver transplantation: a pilot study(SPRINGERNATURE, 2021-08-24)OBJECTIVE: We performed a single-center double-blinded, randomized trial to investigate the hemodynamic effects of IV paracetamol in patients with chronic liver disease (CLD) undergoing liver transplantation surgery. Patients with CLD are particularly susceptible to hemodynamic derangements given their low systemic vascular resistance state. Accordingly, hypotension is common in this setting. The hemodynamic effects of IV paracetamol in patients undergoing elective liver transplantation are unknown, therefore we evaluated whether the intraoperative administration of IV paracetamol in patients with chronic liver disease undergoing liver transplantation results in adverse hemodynamic effects. The primary end point was a change in systolic blood pressure 30-min after the preoperative infusion. RESULTS: Twenty-four participants undergoing liver transplantation surgery were randomly assigned to receive a single bolus of IV paracetamol (1 g paracetamol + 3.91 g mannitol per 100 mL) (n = 12) or placebo (0.9% Saline 100 mL) (n = 12). All participants completed their study intervention, and there were no breaches or violations of the trial protocol. Baseline characteristics were similar in both groups. There were no significant differences regarding surgical duration, intraoperative use of fluids, and intraoperative noradrenaline use. After the administration of paracetamol there were no significant differences observed in blood pressure or other hemodynamic parameters when compared to placebo.
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ItemThe effects of 0.9% saline versus Plasma-Lyte 148 on renal function as assessed by creatinine concentration in patients undergoing major surgery: A single-centre double-blinded cluster crossover trial(PUBLIC LIBRARY SCIENCE, 2021-05-19)OBJECTIVES: Saline and Plasma-Lyte have different physiochemical contents; consequently, they may differently affect patients' renal function. We compared the effects of fluid therapy with 0.9% saline and with Plasma-Lyte 148 on renal function as assessed by creatinine concentration among patients undergoing major surgery. METHODS: We conducted a prospective, double-blinded cluster crossover trial comparing the effects of the two fluids on major surgery patients. The primary aim was to establish the pilot feasibility, safety and preliminary efficacy evidence base for a large interventional trial to establish whether saline or Plasma-Lyte is the preferred crystalloid fluid for managing major surgery patients. The primary efficacy outcome was the proportion of patients with changes in renal function as assessed by creatinine concentration during their index hospital admission. We used changes in creatinine to define acute kidney injury (AKI) according to the RIFLE criteria. RESULTS: The study was feasible with 100% patient and clinician acceptance. There were no deviations from the trial protocol. After screening, we allocated 602 patients to saline and 458 to Plasma-Lyte. The median (IQR) volume of intraoperative fluid received was 2000 mL (1000:2000) in both groups. Forty-nine saline patients (8.1%) and 49 Plasma-Lyte patients (10.7%) developed a postoperative AKI (adjusted incidence rate ratio [aIRR]: 1.34; 95% CI: 0.93-1.95; p = 0.120). No differences were observed in the development of postoperative complications (aIRR: 0.98; 95% CI: 0.89-1.08) or the severity of the worst complication (aIRR: 1.00; 95% CI: 0.78-1.30). The median (IQR) length of hospital stay was six days (3:11) for the saline group and five days (3:10) for the Plasma-Lyte group (aIRR: 0.85; 95% CI: 0.73-0.98). There were no serious adverse events relating to the trial fluids, nor were there fluid crossover or contamination events. CONCLUSIONS: The study design was feasible to support a future follow-up larger clinical trial. Patients treated with saline did not demonstrate an increased incidence of postoperative AKI (defined as changes in creatinine) compared to those treated with Plasma-Lyte. Our findings imply that clinicians can reasonably use either solution intraoperatively for adult patients undergoing major surgery. TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; ACTRN12613001042730; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364988.
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ItemThe hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study(PUBLIC LIBRARY SCIENCE, 2018-04-16)The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting.
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ItemAnaesthetists' attitudes towards attending the funerals of their patients: A cross-sectional study among Australian and New Zealand anaesthetists(PUBLIC LIBRARY SCIENCE, 2020-11-05)A patient's death can pose significant stress on the family and the treating anaesthetist. Anaesthetists' attitudes about the benefits of and barriers to attending a patient's funeral are unknown. Therefore, we performed a prospective, cross-sectional study to ascertain the frequency of anaesthetists' attendance at a patient's funeral and their perceptions about the benefits and barriers. The primary aim was to investigate the attitudes of anaesthetists towards attending the funeral of a patient. The secondary aims were to examine the perceived benefits of and barriers to attending the funeral and to explore the rate of bonds being formed between anaesthetists, patients and families. Of the 424 anaesthetists who completed the survey (response rate 21.2%), 25 (5.9%) had attended a patient's funeral. Of the participants, 364 (85.9%) rarely formed special bonds with patients or their families; 233 (55%) believed that forming a special bond would increase the likelihood of their attendance. Showing respect to patients or their families was the most commonly perceived benefit of attending a funeral. Participants found expression of personal grief and caring for the patient at the end-of-life and beyond beneficial to themselves and the family. Fear of their attendance being misinterpreted or perceived as not warranted by the family as well as time restraints were barriers for their attendance. Most anaesthetists had never attended a patient's funeral. Few anaesthetists form close relationships with patients or their families. Respect, expression of grief and caring beyond life were perceived benefits of attendance. Families misinterpreting the purpose of attendance or not expecting their attendance and time restraints were commonly perceived barriers. Trial registration: ACTRN 12618000503224.
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ItemAssessment of agreement and interchangeability between the TEG5000 and TEG6S thromboelastography haemostasis analysers: a prospective validation study(BMC, 2019-03-30)BACKGROUND: TEG6S® and TEG5000® (Haemonetics Corp, USA) are haemostasis analysers that measure viscoelasticity properties of whole blood. Both use different mechanisms to assess similar components of the coagulation process. The aim of this study was to assess agreement and interchangeability between the TEG6S and TEG5000 analysers. METHODS: 3.5 mL whole blood was collected from 25 adult patients in a tertiary intensive care unit (ICU). Analysis was performed using TEG6S and TEG5000 haemostatic platforms. Agreement between platforms was measured using Lin's concordance coefficient (Lin's CC), further validated using intraclass correlation coefficients and reduced major axis regression (RMAR). RESULTS: Sixteen (64%) patients were male; mean (range) age: 59yo (23-86). TEG6S and TEG5000 systems were broadly interchangeable. The majority of TEG variables demonstrated almost perfect or substantial agreement and minimal proportional bias (maximum amplitude demonstrated a fixed bias). LY30%, however, demonstrated poor agreement and a proportional bias. Lin's CC coefficients (95% CI, RMAR slope, intercept) between TEG6S and TEG5000 variables were: R time: 0.78 (0.64-0.92, 0.76, 0.92); K time: 0.82 (0.69-0.94, 1.30, - 0.93); alpha angle: 0.79 (0.64-0.95, 1.04, - 1.43); maximum amplitude (MA): 0.90 (0.83-0.96, 0.99, - 5.0); LY30%: 0.34 (0.1-0.58, 0.43, 0.04). CONCLUSIONS: Adult patients with critical illness demonstrate almost perfect agreement in the R time and MA, substantial agreement in K time and alpha angle, but poor agreement in LY30%, as measured by the TEG6S and TEG5000 analysers. With the exception of LY30%, the TEG6S and TEG5000 platforms appear interchangeable. This has important implications for use in clinical practice and multi-site research programs. TRIAL REGISTRATION: ANZCRT number: 12617000062325 , registered 12/Jan17. Retrospectively registered.
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ItemAssessing TEG6S reliability between devices and across multiple time points: A prospective thromboelastography validation study(NATURE PUBLISHING GROUP, 2020-04-27)The TEG6S is a novel haemostasis analyser utilising resonance technology. It offers potentially greater coagulation information and ease of use, however has not been independently validated in a clinical setting. We aimed to determine if the TEG6S is reliable between devices and across time points. We performed a prospective observational study with ethical approval. For interdevice reliability, we performed simultaneous analysis on two TEG6S devices on 25 adult ICU patients. For time point reliability, we performed repeated sampling across five different time points on 15 adult participants. Blood was collected with informed consent, or as standard care, before four-channel citrated kaolin analysis. We observed almost perfect interdevice reliability across all TEG parameters. The Lin's concordance correlation coefficients (95% CI, major axis regression slope, intercept) were R-time: 0.96 (0.92-0.99, 0.88, 0.57); K-time: 0.93 (0.87-0.98, 1.07, 0.00); Alpha Angle: 0.87 (0.78-0.96, 1.20, -14.10); Maximum Amplitude: 0.99 (0.98-0.99, 1.02, -1.38); Clot Lysis: 0.89 (0.82-0.97, 1.20, 0.07). Additionally, we observed moderate-to-high reliability across time points. Demonstrating almost perfect agreement across different devices and moderate-to-high reliability across multiple time points, suggests the TEG6S platform can be used with haemostatic accuracy and generalisability. This has potentially significant implications for clinical practice and multi-site research programs.
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ItemRandomised controlled trial to investigate the relationship between mild hypercapnia and cerebral oxygen saturation in patients undergoing major surgery(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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ItemBereavement practices employed by hospitals and medical practitioners toward attending funeral of patients A systematic review(LIPPINCOTT WILLIAMS & WILKINS, 2019-09)OBJECTIVES: To ascertain bereavement practices offered by hospitals and medical practitioners (MPs), factors that influence the likelihood of MPs' involvement in funeral attendance, the benefits and barriers to attendance to a patient's funeral as perceived by MPs and the rate of attendance to patients' funeral by MPs. DESIGN: MEDLINE (Ovid), Embase, PubMed, and Google Scholar were searched with a systematic search structure for randomized controlled trials, comparative observational studies, case series, cross-sectional studies, editorials, and letters. The search was limited to English only. The study was registered with Prospero (Registration Number: CRD42018095368). RESULTS: A total of 381 articles were identified with 46 articles meeting the inclusion criteria. Of the 46, 16 were editorials and 12 were letters. Eighteen were cross-sectional studies conducted in the United States, Canada, Australia, Israel, and Ireland. Year of publication ranged from 1990 to 2017. Of these, 12 were quantitative, 3 were qualitative, and 3 were mixed-method studies. Two of the cross-sectional studies involved family members of deceased patients while others involved MPs. Bereavement practices offered by hospitals included memorial services, letters, and services provided by bereavement coordinators. Bereavement practices employed by MPs included answering or making phone calls, attending family meetings, and sending condolence letters. MPs' attendance at a patient's funeral was influenced by MPs' gender, age years of experience the medical specialty. Perceived benefits of MPs' attendance at a patient's funeral included providing support to the family, extending the professional relationship, illustrating respect to the patient and the family, resolving guilt and personal growth. Barriers to the attendance included a lack of time, blurring of professional boundaries, personal discomfort with death, emotional arousal, and discouragement by colleagues. General practice had an attendance rate of 71%. Attendance rates for palliative care, oncology, and psychiatrists ranged from 63% to 81%, 7.1% to 67%, and 15% to 67%, respectively. Intensivists had an attendance rate of 22%. CONCLUSION: Several bereavement practices are provided by hospitals and MPs. Funeral attendance is an uncommon bereavement practice. MPs' attitudes toward attending a patient's funeral are understudied in many specialties. Patient factors that influence MPs' participation in bereavement practices are poorly understood.
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ItemIntrathecal morphine is associated with reduction in postoperative opioid requirements and improvement in postoperative analgesia in patients undergoing open liver resection(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 .
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ItemRestrictive intraoperative fluid optimisation algorithm improves outcomes in patients undergoing pancreaticoduodenectomy: A prospective multicentre randomized controlled trial(PUBLIC LIBRARY SCIENCE, 2017-09-07)We aimed to evaluate perioperative outcomes in patients undergoing pancreaticoduodenectomy with or without a cardiac output goal directed therapy (GDT) algorithm. We conducted a multicentre randomised controlled trial in four high volume hepatobiliary-pancreatic surgery centres. We evaluated whether the additional impact of a intraoperative fluid optimisation algorithm would influence the amount of fluid delivered, reduce fluid related complications, and improve length of hospital stay. Fifty-two consecutive adult patients were recruited. The median (IQR) duration of surgery was 8.6 hours (7.1:9.6) in the GDT group vs. 7.8 hours (6.8:9.0) in the usual care group (p = 0.2). Intraoperative fluid balance was 1005mL (475:1873) in the GDT group vs. 3300mL (2474:3874) in the usual care group (p<0.0001). Total volume of fluid administered intraoperatively was also lower in the GDT group: 2050mL (1313:2700) vs. 4088mL (3400:4525), p<0.0001 and vasoactive medications were used more frequently. There were no significant differences in proportions of patients experiencing overall complications (p = 0.179); however, fewer complications occurred in the GDT group: 44 vs. 92 (Incidence Rate Ratio: 0.41; 95%CI 0.24 to 0.69, p = 0.001). Median (IQR) length of hospital stay was 9.5 days (IQR: 7.0, 14.3) in the GDT vs. 12.5 days in the usual care group (IQR: 9.0, 22.3) for an Incidence Rate Ratio 0.64 (95% CI 0.48 to 0.85, p = 0.002). In conclusion, using a surgery-specific, patient-specific goal directed restrictive fluid therapy algorithm in this cohort of patients, can justify using enough fluid without causing oedema, yet as little fluid as possible without causing hypovolaemia i.e. "precision" fluid therapy. Our findings support the use of a perioperative haemodynamic optimization plan that prioritizes preservation of cardiac output and organ perfusion pressure by judicious use of fluid therapy, rational use of vasoactive drugs and timely application of inotropic drugs. They also suggest the need for further larger studies to confirm its findings.