Optimised dosing of vancomycin in critically ill Indigenous Australian patients with severe sepsis.

Vancomycin is a commonly used antibiotic due to the high burden of methicillin-resistant Staphylococcus aureus infections. This study aimed to describe the pharmacokinetics (PK) of vancomycin in Australian Indigenous patients with severe sepsis, and advise an optimal dosing strategy. A population PK study was conducted in a remote Australian intensive care unit (ICU). Serial plasma samples were collected over one to two dosing intervals and assayed by validated chromatography. Concentration-time data collected were analysed using Pmetrics® software. The final population PK model was then used for Monte Carlo dosing simulations to determine optimal loading and intermittent maintenance doses. Fifteen Indigenous subjects were included for analysis with a median (interquartile range, IQR) age, weight and creatinine clearance (CrCL) of 43 (34-46) years, 73 (66-104) kg and 99 (56-139) ml/minute respectively. A two-compartment model described the data adequately. Vancomycin clearance (CL) and volume of distribution of the central compartment (Vc) were described by CrCL and patient weight respectively. Median (IQR) CL, Vc, distribution rate constants from central to peripheral, and from peripheral to central compartments were 4.6 (3.8-5.6) litres per hour, 25.4 (16.1-31.3) litres, 0.46 (0.28-0.52)/hour and 0.25 (0.12-0.37)/hour respectively. No significant interethnic PK differences were observed in comparison to published data. Therapeutic loading doses were significantly dependent on both weight and CrCL, whereas maintenance doses were dependent on CrCL. In the absence of severe renal impairment, initiation of maintenance dose eight hours post-loading dose achieved higher probability of target attainment at 24 hours. This is the first report of vancomycin PK in this patient group.

Prevalence of augmented renal clearance and performance of glomerular filtration estimates in Indigenous Australian patients requiring intensive care admission.

Augmented renal clearance (ARC) refers to the enhanced renal excretion of circulating solute commonly demonstrated in numerous critically ill subgroups. This study aimed to describe the prevalence of ARC in critically ill Indigenous Australian patients and explore the accuracy of commonly employed mathematical estimates of glomerular filtration. We completed a single-centre, prospective, observational study in the intensive care unit (ICU), Alice Springs Hospital, Central Australia. Participants were critically ill adult Indigenous and non-Indigenous Australian patients with a urinary catheter in situ. Exclusion criteria were anuria, pregnancy or the requirement for renal replacement therapy. Daily eight-hour measured creatinine clearances (CrCLm) were collected throughout the ICU stay. ARC was defined by a CrCLm ≥130 ml/min/1.73 m2. The Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations were also used to calculate mathematical estimates for comparison. In total, 131 patients were recruited (97 Indigenous, 34 non-Indigenous) and 445 samples were collected. The median (range) CrCLm was 93.0 (5.14 to 205.2) and 90.4 (18.7 to 206.8) ml/min/1.73 m2 in Indigenous and non-Indigenous patients, respectively. Thirty-one of 97 (32%) Indigenous patients manifested ARC, compared to 7 of 34 (21%) non-Indigenous patients (P=0.21). Younger age, major surgery, higher baseline renal function and an absence of diabetes were all associated with ARC. Both mathematical estimates manifest limited accuracy. ARC was prevalent in critically ill Indigenous patients, which places them at significant risk of underdosing with renally excreted drugs. CrCLm should be obtained wherever possible to ensure accurate dosing.

The impact of alcohol-related admissions on resource use in critically ill patients from 2009 to 2015: an observational study.

Excessive alcohol use is associated with increased health care utilisation and increased mortality. This observational study sought to identify the proportion of patients admitted with a critical illness in which alcohol misuse contributed, and to examine the resource use for this group. We performed an observational retrospective database review of all admissions to the Alice Springs Hospital intensive care unit (ICU) between 1 January 2009 and 31 December 2015. The Alice Springs Hospital ICU is a ten-bed unit located in Central Australia, with approximately 600 admissions annually. The per capita consumption of alcohol in Central Australia is approximately 1.5 times the national average. The primary aim was to determine the proportion of admissions to intensive care in which alcohol misuse was identified as a contributing cause. Secondary aims examined resource utilisation including ICU and hospital length of stay, need for and duration of mechanical ventilation, and ICU re-admission. There were 3,768 admissions involving 2,670 individual patients. Of these admissions 947 (25%) were associated with alcohol misuse. Admissions associated with alcohol were significantly more likely to require mechanical ventilation (30% versus 20%, P <0.01), and had a significantly longer ICU length of stay (2.1 versus 1.9 days, P <0.05). The proportion of admissions in which alcohol misuse was implicated is amongst the highest in the published literature. The results of this study should drive further policy change directed at harm minimisation, and warrant more detailed epidemiological work at both a local and national level.

Lipid profiles and persisting inflammation following critical illness in a central Australian population: a prospective longitudinal observational study.

No published data exist following the changes in lipid profile during and after an episode of acute illness for the Australian Indigenous population. This paper presents data focusing on lipid profiles and inflammatory markers in a group of survivors of critical illness in Central Australia, prospectively recruited to a larger trial exploring the medium-term sequelae of an intensive care unit admission. This data confirm that lipid profiles in acute illness are deranged, and that recovery may differ between indigenous and non-indigenous populations.

Paediatric day stay tonsillectomy service: development and audit.

Day stay paediatric tonsillectomy is well established in many parts of the world but not in Australia. This audit presents the protocol and results of the first one hundred and twenty-five patients managed this way at our hospital. Patients assessed as being at low risk of postoperative complications were offered the procedure as a day patient. All patients had a standardized relaxant anaesthetic technique with an intraoperative opioid and antiemetics. The patients were observed for six hours postoperatively in the Day Stay Unit and contacted the day following surgery to assess any problems. The overall incidence of postoperative vomiting was 15.6%. Two patients required overnight admission. One child was re-admitted on day four for delayed postoperative haemorrhage. Forty-four of the first forty-nine patients' parents were contacted four to six weeks later to assess their experiences of the process. Although approximately three-quarters of the parents rated their child's pain as moderate or severe at some stage, all but one felt the analgesic regimen was good or adequate. Eighty per cent were satisfied with having the surgery as a day stay procedure.

Superior vena cava obstruction and liver transplantation in a child.

We report a case of superior vena cava obstruction in a child, which was probably secondary to long-term central venous cannulation. The obstruction was asymptomatic preoperatively, but became evident during liver transplantation, and complicated the intraoperative management. There is one other case report of this occurring in an adult in similar circumstances, and we believe that ours is the first report of such a presentation in the paediatric age group.

Early morphological changes in blood capillaries of mouse duodenal villi induced by X-irradiation.

The mouse has been used extensively as a model for radiobiological studies. In particular, the cellular compartments of the intestinal villi have been examined, in an effort to gain an understanding of the gastrointestinal disturbances which follow radiotherapy of the abdomen. The response of the blood vessels has been, however, largely neglected. This paper examines the early response of the duodenal capillaries to an X-ray dose of 10 Gy using conventional light and transmission electron microscopy. The villous capillaries were examined at 6 h, 1 day and 3 days after treatment. The results showed that the capillaries responded to X-irradiation within 6 h. exhibiting marked vasodilation similar to that observed in acute inflammation. Significantly there was no ultrastructural evidence of endothelial cell disruption or loss of junctional attachment between the cells, but the characteristic fenestrae of these vessels were less apparent than in the controls. One day after treatment the capillaries had become constricted, with many vessels totally non-patent. The cytoplasm and nuclei of the endothelial cells showed changes consistent with vascular damage, such as nuclear shape alterations and luminal cytoplasmic projections. Three days after treatment there was variation in the capillary patency, as some vessels showed signs of incipient necrosis whilst others were relatively normal in appearance. The results suggest that the early vascular response typically involves a phase of vasodilation followed by constriction within the first 24 h after treatment, a finding consistent with the radiation response of skin capillaries in what has been described as 'transient erythema'. The ultrastructural changes associated with the phasic changes in patency did not suggest large scale endothelial death, but rather alteration of the functional capacity of the vessels which may in turn affect the other cell populations in the villi.