10 research outputs found
Long-Term Outcomes in Survivors of Critical Illness and Interaction with Glucose Metabolism
Even after surviving critical illness, many patients who are discharged from an Intensive Care Unit (ICU) die or suffer major morbidity. Diabetes is a risk factor for critical illness and its severity and critical illness also affects immediate glucose metabolism. In addition, substantial similarities exist between complications of critical illness and diabetes (nephropathy and neuropathy), such that critical illness may exacerbate complications of diabetes. Hitherto, the longer-term interaction between critical illness, glucose metabolism and outcomes had been scarcely evaluated. The aims of this thesis were to 1) determine long-term outcomes and evaluate follow-up care of ICU survivors with diabetes, 2) optimise glycaemic targets for critically patients with diabetes during the entire hospitalisation, 3) evaluate the long-term impact of stress hyperglycaemia, and 4) evaluate effects of critical illness on the autonomic nervous system, particularly with respect to nutrient intake and glucose metabolism. A large state-wide epidemiological study was conducted (Chapter 2.2) which identified that ICU survivors with diabetes experience greater loss of life-years after hospital discharge than those without diabetes. There is, therefore, a rationale to improve outcomes in this group. A novel intervention (an intensivist-endocrinologist ICU follow-up clinic) was created and a randomised controlled feasibility study was designed (Chapter 2.3). Although patients perceived that the intervention enhanced their recovery, the study did not meet feasibility criteria because of incomplete outcome data with high death rates. Survivors also experienced poor functional outcomes and high healthcare use (Chapter 2.4). In order to personalise glycaemic control during hospitalisation, it is necessary to rapidly determine premorbid glycaemia. A single centre observational study was undertaken to establish that point-of-care glycated haemoglobin testing is both accurate and feasible in ICU (Chapter 3.2). Despite substantial focus on glycaemia during ICU admission, data following ICU discharge are limited. Combined continuous glucose and electrocardiograph monitoring was utilised in a two-centre prospective cohort study to evaluate glycaemia and cardiac arrhythmias in patients prescribed insulin after ICU discharge (Chapter 3.3). Hypoglycaemia occurred frequently, was often nocturnal and asymptomatic, and increased the risk of bradycardia. These findings suggest that cautious prescription of insulin upon ICU discharge is necessary. Stress hyperglycaemia occurs frequently during critical illness in those without diabetes, but has traditionally been considered a transient phenomenon. A systematic review and metaanalysis was undertaken ascertaining that stress hyperglycaemia is associated with subsequent increased risk of both prediabetes and diabetes (Chapter 4.2). The potential mechanisms underlying this relationship and clinical implications were also addressed (Chapter 4.3). Autonomic neuropathy was evaluated in older patients at 3 and 12 months after ICU discharge using a longitudinal cohort study design (Chapter 5). Autonomic function was assessed specifically in the context of nutrient ingestion and glycaemia. Postprandial hypotension occurred frequently in this group and increased the risk of falls. In summary, this thesis has contributed to the understanding of long-term outcomes of ICU survivors with diabetes, as well as glycaemia and autonomic function after ICU discharge, and has evaluated a novel approach to follow-up care in survivors of critical illness with diabetes.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 202
Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries
Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20
[1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
Additional file 2: of Stress hyperglycaemia in critically ill patients and the subsequent risk of diabetes: a systematic review and meta-analysis
Search strategies. (DOCX 17 kb
Clinician and patient identified solutions to reduce the fragmentation of post-ICU care in Australia
BackgroundCritical care survivors experience multiple care transitions, with no formal follow-up care pathway.Research QuestionWhat are the potential solutions to improve the communication between treating teams and integration of care following an Intensive Care Unit (ICU) admission – from the perspective of patients, their caregivers, intensivists, and General Practitioners (GPs) from diverse socioeconomic areas?Study Design& Methods: Qualitative design using semi-structured interviews with intensivists, GPs, and patients and caregivers. Framework Analysis was used to analyse data, and to identify solutions to improve the integration of care post-hospital discharge. Patients were previously mechanically ventilated for >24 hours in ICU and had access to a video-enabled device. Clinicians were recruited from hospital networks and a state-wide GP network.ResultsForty-six interviews with clinicians, patients and caregivers were completed (15 Intensivists, 8 GPs, 15 patients and 8 caregivers). Three higher-level feedback loops were identified, that comprised of ten themes. Feedback loop 1: ICU and primary care collaboration: 1. Developing collaborative relationships between the ICU and primary care, 2. Providing interprofessional education and resources to support primary care, 3. Improving role clarity for patient follow-up care; Feedback loop 2: Developing mechanisms for improved communication across the care continuum: 4. Timely, concise information sharing with primary care on post-ICU recovery, 5. Survivorship focused information sharing across the continuum of care, 6. Empowering patients and caregivers in self-management; 7. Creation of a care coordinator role for survivors; and Feedback loop 3: Learning from post-ICU outcomes to improve future care: 8. Developingcomprehensive post-ICU care pathways, 9. Enhancing support for patients after hospital, 10. Integration of post-ICU outcomes within the ICU to improve clinician morale and understanding.InterpretationPractical solutions to enhance the quality of survivorship for critical care survivors and their caregivers were identified. These themes are mapped to a novel conceptual model that includes key feedback loops for health system improvements and foci for future interventional trials to improve ICU survivorship outcomes
Pharmacokinetic data support 6-hourly dosing of intravenous vitamin C to critically ill patients with septic shock.
OBJECTIVES
To study vitamin C pharmacokinetics in septic shock.
DESIGN
Prospective pharmacokinetic study.
SETTING
Two intensive care units.
PARTICIPANTS
Twenty-one patients with septic shock enrolled in a randomised trial of high dose vitamin C therapy in septic shock.
INTERVENTION
Patients received 1.5 g intravenous vitamin C every 6 hours. Plasma samples were obtained before and at 1, 4 and 6 hours after drug administration, and vitamin C concentrations were measured by high performance liquid chromatography.
MAIN OUTCOME MEASURES
Clearance, volume of distribution, and half-life were calculated using noncompartmental analysis. Data are presented as median (interquartile range [IQR]).
RESULTS
Of the 11 participants who had plasma collected before any intravenous vitamin C administration, two (18%) were deficient (concentrations < 11 μmol/L) and three (27%) had hypovitaminosis C (concentrations between 11 and 23 μmol/L), with a median concentration 28 μmol/L (IQR, 11-44 μmol/L). Volume of distribution was 23.3 L (IQR, 21.9-27.8 L), clearance 5.2 L/h (IQR, 3.3-5.4 L/h), and half-life 4.3 h (IQR, 2.6-7.5 h). For the participants who had received at least one dose of intravenous vitamin C before sampling, T0 concentration was 258 μmol/L (IQR, 162- 301 μmol/L). Pharmacokinetic parameters for subsequent doses were a median volume of distribution 39.9 L (IQR, 31.4-44.4 L), clearance 3.6 L/h (IQR, 2.6-6.5 L/h), and half-life 6.9 h (IQR, 5.7-8.5 h).
CONCLUSION
Intravenous vitamin C (1.5 g every 6 hours) corrects vitamin C deficiency and hypovitaminosis C and provides an appropriate dosing schedule to achieve and maintain normal or elevated vitamin C levels in septic shock
Intensity of early correction of hyperglycaemia and outcome of critically ill patients with diabetic ketoacidosis
Objectives: To determine the impact of the intensity of early correction of hyperglycaemia on outcomes in patients with diabetic ketoacidosis (DKA) admitted to the intensive care unit. Methods: We studied adult patients with DKA admitted to 171 ICUs in Australia and New Zealand from 2000 to 2013. We used their blood glucose levels (BGLs) in the first 24 hours after ICU admission to determine whether intensive early correction of hyperglycemia to 180 mg/dL as recommended by DKA-specific guidelines. Results: Among 8553 patients, intensive early correction of BGL was applied to 605 patients (7.1 %). A greater proportion of these patients experienced hypoglycaemia (20.2% v 9.1%; P < 0.001) and/or hypo-osmolarity (29.4% v 22.0%; P < 0.001), but not hypokalaemia (16.7% v 15.6%; P = 0.47). Overall, 11 patients (1.8%) in the intensive correction group and 112 patients (1.4%) in the partial correction group died (P = 0.42). However, after adjustment for illness severity, partial early correction of BGL was independently associated with a lower risk of hypoglycaemia (odds ratio [OR], 0.38; 95% CI, 0.30-0.48; P < 0.001), lower risk of hypo-osmolarity (OR, 0.80; 95% CI, 0.65-0.98; P < 0.03) and lower risk of death (OR, 0.44; 95% CI, 0.22-0.86; P = 0.02). Conclusions: In a large cohort of patients with DKA, partial early correction of BGL according to DKA-specific guidelines, when compared with intensive early correction of BGL, was independently associated with a lower risk of hypoglycaemia, hypo-osmolarity and death