Anaesthesia and Intensive Care publications

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Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial
(Springer-Verlag, 2021) Arabi, Y.M.; Gordon, A.C.; Derde, L.P.G.; Nichol, A.D.; Murthy, S.; Beidh, F.A.; Annane, D.; Swaidan, L.A.; Beane, A.; Beasley, R.; Berry, L.R.; Bhimani, Z.; Bonten, M.J.M.; Bradbury, C.A.; Brunkhorst, F.M.; Buxton, M.; Buzgau, A.; Cheng, A.; De Jong, M.; Detry, M.A.; et al.
Purpose: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). Methods: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. Results: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (– 1 to 15), 0 (– 1 to 9) and—1 (– 1 to 7), respectively, compared to 6 (– 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ supportfree days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). Conclusion: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.
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Hospital variability of postoperative sepsis and sepsis-related mortality after elective coronary artery bypass grafting surgery
(Elsevier, 2018) Ou, L.; Chen, J.; Flabouris, A.; Hillman, K.; Parr, M.; Bellomo, R.
Purpose
Hospital variability of postoperative sepsis and sepsis-related mortality after elective CABG surgery was not known in Australia.
Material and methods
Population-based analysis of all elective patients who underwent CABG surgery in public and private hospitals between 2007 and 2014 using linked data from the state-wide Admitted Patient Data Collection and the NSW Registry of Births, Deaths, and Marriages.
Results
We identified 18,928 (9464 pairs) matched patients who had elective CABG surgery in public hospitals (n = 9) and private hospitals (n = 13) during the study period. When compared to public hospital patients, private hospital patients had a significantly lower rate of post-CABG sepsis (13.3 vs 20.4 per 1000 admissions, P < 0.001; treatment effects: -7.1, 95%CI: -11.1 to -3.3), a lower in-hospital mortality rate (6.1 vs 9.9 per 1000 admissions, P = 0.006; treatment effects: -3.8, 95%CI: -6.5 to -1.1), and a lower rate of 30-day readmission (11.9% vs 13.9%, P < 0.001; treatment effects: -2.0%, 95%CI: -3.1% to -1.0%). In addition, for both public and private hospital groups, there were significant differences for all outcomes when comparing the worst and best performance quintile hospitals.
Conclusions
Hospital variability of postoperative sepsis, in-hospital mortality and readmission after elective CABG existed between and within public and private hospitals.
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Critical illness is associated with impaired gallbladder emptying as assessed by 3D ultrasound
(Lippincott Williams & Wilkins, 2016) Plummer, M.; Kar, P.; Cousins, C.; Hausken, T.; Lange, K.; Chapman, M.; Jones, K.; Horowitz, M.; Deane, A.
Objective: To quantify gallbladder dysfunction during critical illness. Design: Prospective observational comparison study of nutrient-stimulated gallbladder emptying in health and critical illness. Setting: Single-centre mixed medical/surgical ICU. Patients: Twenty-four mechanically ventilated critically ill patients suitable to receive enteral nutrition were compared with 12 healthy subjects. Interventions: Participants were studied after an 8-hour fast. Between 0 and 120 minutes, high-fat nutrient (20% intralipid) was infused via a postpyloric catheter into the duodenum at 2 kcal/min. Measurements and Main Results: Three-dimensional images of the gallbladder were acquired at 30-minute intervals from -30 to 180 minutes. Ejection fraction (%) was calculated as changes between 0 and 120 minutes. Blood samples were obtained at 30-minute intervals for plasma cholecystokinin. Data are mean (SD) or median [interquartile range]. In the critically ill, fasting gallbladder volumes (critically ill, 61 mL [36-100 mL] vs healthy, 22 mL [15-25] mL; p < 0.001] and wall thickness (0.45 mm [0.15 mm] vs 0.26 mm [0.08 mm]; p < 0.001] were substantially greater, and sludge was evident in the majority of patients (71% vs 0%). Nutrient-stimulated emptying was incomplete in the critically ill after 120 minutes but was essentially complete in the healthy individuals (22 mL [9-66 mL] vs 4 mL [3-5 mL]; p < 0.01]. In five critically ill patients (21%), there was no change in gallbladder volume in response to nutrient, and overall ejection fraction was reduced in the critically ill (50% [8-83%] vs 77 [72-84%]; p = 0.01]. There were no differences in fasting or incremental cholecystokinin concentrations. Conclusions: Fasted critically ill patients have larger, thicker-walled gallbladders than healthy subjects and nutrient-stimulated gallbladder emptying is impaired with "gallbladder paresis" occurring in approximately 20%.
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The timing of discharge from the Intensive Care Unit and subsequent mortality: a prospective, multicenter study
(American Thoracic Society, 2015) Santamaria, J.; Duke, G.; Pilcher, D.; Cooper, D.; Moran, J.; Bellomo, R.
Rationale: Previous studies suggested an association between after-hours intensive care unit (ICU) discharge and increased hospital mortality. Their retrospective design and lack of correction for patient factors present at the time of discharge make this association problematic. Objectives: To determine factors independently associated with mortality after ICU discharge. Methods: This was a prospective, multicenter, binational observational study involving 40 ICUs in Australia and New Zealand. Participants were consecutive adult patients discharged alive from the ICU between September 2009 and February 2010. Measurements and Main Results: We studied 10,211 patients discharged alive from the ICU. Median age was 63 years (interquartile range, 49-74), 6,224 (61%) were male, 5,707 (56%) required mechanical ventilation, and their median Acute Physiology and Chronic Health Evaluation III risk of death was 9% (interquartile range, 3-25%). A total of 8,539 (83.6%) patients were discharged in-hours (06:00-18:00) and 1,672 (16.4%) after-hours (18:00-06:00). Of these, 408 (4.8%) and 124 (7.4%), respectively, subsequently died in hospital (P < 0.001). After risk adjustment for markers of illness severity at time of ICU discharge including limitations of medical therapy (LOMT) orders, the time of discharge was no longer a significant predictor of mortality. The presence of a LOMT order was the strongest predictor of death (odds ratio, 35.4; 95% confidence interval, 27.5-45.6). CONCLUSIONS: In this large, prospective, multicenter, binational observational study, we found that patient status at ICU discharge, particularly the presence of LOMT orders, was the chief predictor of hospital survival. In contrast to previous studies, the timing of discharge did not have an independent association with mortality.
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In vivo microdialysis to determine subcutaneous interstitial fluid penetration and pharmacokinetics of fluconazole in intensive care unit patients with sepsis
(American Society for Microbiology, 2016) Sinnollareddy, M.G.; Roberts, M.S.; Lipman, J.; Lassig-Smith, M.; Starr, T.; Robertson, T.; Peake, S.L.; Roberts, J.A.
The objective of the study was to describe the subcutaneous interstitial fluid (ISF) pharmacokinetics of fluconazole in critically ill patients with sepsis. This prospective observational study was conducted at two tertiary intensive care units in Australia. Serial fluconazole concentrations were measured over 24 h in plasma and subcutaneous ISF using microdialysis. The concentrations in plasma and microdialysate were measured using a validated high-performance liquid chromatography system with electrospray mass spectrometer detector method. Noncompartmental pharmacokinetic analysis was performed. Twelve critically ill patients with sepsis were enrolled. The mean in vivo fluconazole recovery rates ± standard deviation (SD) for microdialysis were 51.4% ± 16.1% with a mean (±SD) fluconazole ISF penetration ratio of 0.52 ± 0.30 (coefficient of variation, 58%). The median free plasma area under the concentration-time curve from 0 to 24 h (AUC0-24) was significantly higher than the median ISF AUC0-24 (340.4 versus 141.1 mg · h/liter; P = 0.004). There was no statistical difference in median fluconazole ISF penetration between patients receiving and not receiving vasopressors (median, 0.28 versus 0.78; P = 0.106). Both minimum and the maximum concentrations of drug in serum (Cmax and Cmin) showed a significant correlation with the fluconazole plasma exposure (Cmax, R(2) = 0.86, P < 0.0001; Cmin, R(2) = 0.75, P < 0.001). Our data suggest that fluconazole was distributed variably, but incompletely, from plasma into subcutaneous interstitial fluid in this cohort of critically ill patients with sepsis. Given the variability of fluconazole interstitial fluid exposures and lack of clinically identifiable factors by which to recognize patients with reduced distribution/exposure, we suggest higher than standard doses to ensure that drug exposure is adequate at the site of infection.
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Stopping vs. continuing aspirin before coronary artery surgery
(Massachusetts Medical Society, 2016) Myles, P.; Smith, J.; Forbes, A.; Silbert, B.; Jayarajah, M.; Painter, T.; Cooper, D.; Marasco, S.; McNeil, J.; Bussières, J.; Wallace, S.
BACKGROUND Most patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infarction, stroke, and death. Aspirin poses a risk of bleeding in patients undergoing surgery, but it is unclear whether aspirin should be stopped before coronary artery surgery. METHODS We used a 2-by-2 factorial trial design to randomly assign patients who were scheduled to undergo coronary artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin trial are reported here. Patients were randomly assigned to receive 100 mg of aspirin or matched placebo preoperatively. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS Among 5784 eligible patients, 2100 were enrolled; 1047 were randomly assigned to receive aspirin and 1053 to receive placebo. A primary outcome event occurred in 202 patients in the aspirin group (19.3%) and in 215 patients in the placebo group (20.4%) (relative risk, 0.94; 95% confidence interval, 0.80 to 1.12; P = 0.55). Major hemorrhage leading to reoperation occurred in 1.8% of patients in the aspirin group and in 2.1% of patients in the placebo group (P = 0.75), and cardiac tamponade occurred at rates of 1.1% and 0.4%, respectively (P = 0.08). CONCLUSIONS Among patients undergoing coronary artery surgery, the administration of preoperative aspirin resulted in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo. (Funded by the Australian National Health and Medical Research Council and others; Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.)
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Preanesthetic nurse communication with children and parents - an observational study
(Wiley, 2015) Perry, C.; Samuelsson, C.; Cyna, A.; Bosenberg, A.
The impact of communication within the perioperative period is an area of increasing research interest. Suggestions are phrases or actions that can lead to subconscious nonvolitional changes in patient perception, mood, and/or behavior. Statements functioning as suggestions may induce positive or negative perceptual responses and experiences. Children and anxious patients are particularly responsive to the effects of suggestion. We aimed to identify positively and negatively worded statements used during the provision of preoperative information by nursing staff in a tertiary referral center for pediatric care.Audio recordings of preoperative consultations between nurses, children, and their parents were made between February and May 2014. Two researchers independently reviewed the transcripts and identified positively and negatively worded suggestions. Examples of negative suggestions were, 'he is going to be sore for a week or two' or 'normal to feel a bit sick....', and a positive suggestion was 'so she will be feeling quite comfortable...'.There were 51 consultations transcribed and analyzed. Of the 130 suggestions independently agreed by both researchers to be either positive or negative, 40 were identified as positive (31%) and 90 negative (69%). Commonly occurring negative suggestions described: pain in 21 consultations (41%); nausea and sickness in 19 (37%); and irritability or agitation in nine (18%). Positive suggestions included a description of a return of normal activities such as eating and drinking in 14 (28%), comfort in nine (18%), and well-being in nine (18%). Twelve consultations (24%) contained only negative suggestions, while four (8%) had only positive suggestions.This is the first prospective observational study investigating the language used by nurses during the preoperative child-parent encounter. Suggestions for negative perceptual experiences were frequently used during the preoperative nurse consultations. Education of nurses regarding awareness and understanding of negative suggestions and their potential adverse effects is recommended.
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Cranial nerve injuries with supraglottic airway devices: a systematic review of published case reports and series
(Wiley, 2015) Thiruvenkatarajan, V.; Van Wijk, R.; Rajbhoj, A.
Cranial nerve injuries are unusual complications of supraglottic airway use. Branches of the trigeminal, glossopharyngeal, vagus and the hypoglossal nerve may all be injured. We performed a systematic review of published case reports and case series of cranial nerve injury from the use of supraglottic airway devices. Lingual nerve injury was the most commonly reported (22 patients), followed by recurrent laryngeal (17 patients), hypoglossal (11 patients), glossopharyngeal (three patients), inferior alveolar (two patients) and infra-orbital (one patient). Injury is generally thought to result from pressure neuropraxia. Contributing factors may include: an inappropriate size or misplacement of the device; patient position; overinflation of the device cuff; and poor technique. Injuries other than to the recurrent laryngeal nerve are usually mild and self-limiting. Understanding the diverse presentation of cranial nerve injuries helps to distinguish them from other complications and assists in their management.
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Acute pain management: a practical guide
(W.B. Saunders Limited, 2001) Macintyre, P.E.; Ready, L.B.
This second edition has been extensively revised and updated throughout, with the addition of three new chapters and a section of multiple choice questions to aid with examination preparation.
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Nerve sheath catheter analgesia for forequarter amputation in paediatric oncology patients
(Australian Society of Anaesthetists, 2013) Kaddoum, R.N.; Burgoyne, L.L.; Pereiras, L.A.; Germain, M.; Neel, M.; Anghelescu, D.L.
In a single centre over two years, four children (7 to 10 years old) with upper limb osteosarcoma underwent chemotherapy followed by forequarter amputation. All patients had preoperative pain and were treated with gabapentin. Nerve sheath catheters were placed in the brachial plexus intraoperatively and left in situ for five to 14 days. After surgery, all patients received local anaesthetic infused via nerve sheath catheters as part of a multimodal analgesia technique. Three of the four patients were successfully treated as outpatients with the nerve sheath catheters in situ. All four children experienced phantom limb pain; however, it did not persist beyond four weeks in any patient.
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Acute pain management: a practical guide
(Saunders Elsevier, 2007) Macintyre, P.E.; Schug, S.A.
This is a new edition of a highly successful practical guide to acute pain management in the adult patient.
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Acute pain management: a practical guide
(CRC Press, 2015) Macintyre, P.E.; Schug, S.A.
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Stress ulceration: prevalence, pathology and association with adverse outcomes
(BioMed Central, 2014) Plummer, M.; Blaser, A.; Deane, A.
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Subjective and objective experience of pain
(Blackwell Publishing, 2013) Tan, S.; Cyna, A.
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Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis
(BMJ Group, 2008) Peter, J.; John, P.; Graham, P.; Moran, J.; George, I.; Bersten, A.
Objective: To systematically review the efficacy of steroids in the prevention of acute respiratory distress syndrome (ARDS) in critically ill adults, and treatment for established ARDS. Data sources: Search of randomised controlled trials (1966-April 2007) of PubMed, Cochrane central register of controlled trials, Cochrane database of systematic reviews, American College of Physicians Journal Club, health technology assessment database, and database of abstracts of reviews of effects. Data extraction: Two investigators independently assessed trials for inclusion and extracted data into standardised forms; differences were resolved by consensus. Data synthesis: Steroid efficacy was assessed through a Bayesian hierarchical model for comparing the odds of developing ARDS and mortality (both expressed as odds ratio with 95% credible interval) and duration of ventilator free days, assessed as mean difference. Bayesian outcome probabilities were calculated as the probability that the odds ratio would be ≥1 or the probability that the mean difference would be ≥0. Nine randomised trials using variable dose and duration of steroids were identified. Preventive steroids (four studies) were associated with a trend to increase both the odds of patients developing ARDS (odds ratio 1.55, 95% credible interval 0.58 to 4.05; P(odds ratio ≥1)=86.6%), and the risk of mortality in those who subsequently developed ARDS (three studies, odds ratio 1.52, 95% credible interval 0.30 to 5.94; P(odds ratio ≥1)=72.8%). Steroid administration after onset of ARDS (five studies) was associated with a trend towards reduction in mortality (odds ratio 0.62, 95% credible interval 0.23 to 1.26; P(odds ratio ≥1)=6.8%). Steroid therapy increased the number of ventilator free days compared with controls (three studies, mean difference 4.05 days, 95% credible interval 0.22 to 8.71; P(mean difference ≥0)=97.9%). Steroids were not associated with increase in risk of infection. Conclusions: A definitive role of corticosteroids in the treatment of ARDS in adults is not established. A possibility of reduced mortality and increased ventilator free days with steroids started after the onset of ARDS was suggested. Preventive steroids possibly increase the incidence of ARDS in critically ill adults.
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An alternative way of managing acute pain in patients who are in buprenorphine opioid substitution therapy programs
(Blackwell Science Ltd, 2013) Huxtable, C.; Macintyre, P.
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Tracheal extubation under deep sevoflurane anesthesia: a novel strategy for weaning difficulties in intensive care
(Medknow Publications and Media Pvt Ltd, 2013) Sethi, R.; Mahon, S.
Various criteria for weaning patients from ventilators in intensive care have been widely published. These criteria are increasingly incorporated into guidelines, protocols, and more recently, care pathways. We present a case where a patient's lungs were ventilated for 4 days with an infective exacerbation of chronic obstructive pulmonary disease (COPD). We successfully weaned off mechanical ventilation and rapidly extubated the patient's trachea utilizing deep sevoflurane anesthesia. Published weaning indices suggest that this would have been an inappropriate course of action at the time. However, our patient clearly benefited and avoided the need for tracheostomy and prolonged ventilation.
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The gut-brain axis in the critically ill: is glucagon-like peptide-1 protective in neurocritical care?
(Current Science Ltd, 2013) Plummer, M.; Meier, J.; Deane, A.
Enteral nutrient is a potent glucagon-like peptide-1 (GLP-1) secretagogue. In vitro and animal studies indicate that GLP-1 has immune-modulatory and neuroprotective effects. To determine whether these immune-modulatory and neuroprotective effects of GLP-1 are beneficial in the critically ill, studies achieving pharmacological GLP-1 concentrations are warranted.
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Epidural versus continuous transversus abdominis plane catheter technique for postoperative analgesia after abdominal surgery
(Australian Soc Anaesthetists, 2013) Rao, V.; van Wijk, R.; Moran, J.; Miller, D.
Transversus abdominis plane block is an effective postoperative analgesic technique after abdominal surgery, but no study has compared continuous transversus abdominis plane block with continuous epidural analgesia. We designed a randomised controlled trial comparing these techniques for major abdominal surgery. Patients in the epidural group received a bolus of 8 to 15 ml of ropivacaine 0.2% and an infusion of 5 to 15 ml/hour and the transversus abdominis plane block group a bolus dose of 20 ml of ropivacaine 0.375% bilaterally and an infusion of 0.2% ropivacaine 8 ml/hour bilaterally, for three days. Both groups received paracetamol and patient controlled analgesia with fentanyl for three days. Primary outcomes were numerical rating scores for pain (rest and dynamic over 72 hours) and total fentanyl use; complications and satisfaction scores were also noted. The study was terminated early after 42 patients had been randomised (epidural n=19; transversus abdominis plane block n=22; one excluded). No differences were found in regards to point pain scores or scores over time, either immediately postoperatively or in surgical wards; total fentanyl requirement and Likert satisfaction scores were also similar in both groups. In this underpowered study we found comparable results between continuous transversus abdominis plane technique and epidural analgesia in regard to pain, analgesic use and satisfaction after abdominal surgery. To confirm this finding, randomised trials with larger numbers of participants are needed.
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Sodium administration in critically ill patients in Australia and New Zealand: A multicentre point prevalence study
(Australasian Academy of Critical Care Medicine, 2013) Bihari, S.; Peake, S.; Seppelt, I.; Williams, P.; Bersten, A.
BACKGROUND: Inadvertent sodium administration in excess of recommended daily requirements has been reported during routine care of critically ill patients. AIM: To determine the amount and sources of sodium administered in Australian and New Zealand intensive care units. DESIGN, SETTING AND PARTICIPANTS: Prospective, observational, single-day, point prevalence survey conducted in 46 Australian and New Zealand ICUs on 21 September 2011. All patients present in ICU at 10 am and not receiving an oral diet on the study day were evaluated. Demographic data, ICU admission diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II score and sources of sodium administration over the study day were recorded. RESULTS: 356 patients (64% male) were enrolled. Mean (SD) age and weight were 58.5 years (18.0 years) and 81.6 kg (24.0 kg), respectively. Mean ICU admission APACHE II score was 20 (SD, 8). Overall median (interquartile range [IQR]) sodium administration was 224.5 mmol (IQR, 144.9-367.6 mmol), or 2.8 mmol/kg (IQR, 1.6-4.7 mmol/kg). Among patients who were on Day 2-10 of their ICU admission on the study day, sodium sources and amounts administered were: i) maintenance or replacement intravenous (IV) infusions, 69.3mmol; 30.9% of all sodium sources; ii) IV fluid boluses, 36.5 mmol; 16.3%; iii) IV drug boluses, 27.6 mmol; 12.3%; iv) enteral nutrition, 26.5 mmol; 11.8%; v) IV drug infusions, 19.3 mmol; 8.6%; vi) IV flushes, 16.6mmol; 7.4%; vii) blood products, 13.5 mmol; 6%; viii) IV antimicrobials, 11.2mmol; 5%; and ix) parenteral nutrition, 4.3 mmol; 1.9%. Factors associated with sodium administration were site (P = 0.04), age (P < 0.001), administered fluid (P = 0.03) and day of ICU stay (P = 0.01) (multiple linear regression). CONCLUSION: This point prevalence study suggests that sodium administration in excess of recommended daily requirements may be common in Australia and New Zealand ICUs. The main sodium source was IV maintenance fluids, followed by fluid boluses and drug boluses.

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