Priya Nair

Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome.

CONTEXT The novel influenza A(H1N1) pandemic affected Australia and New Zealand during the 2009 southern hemisphere winter. It caused an epidemic of critical illness and some patients developed severe acute respiratory distress syndrome (ARDS) and were treated with extracorporeal membrane oxygenation (ECMO). OBJECTIVES To describe the characteristics of all patients with 2009 influenza A(H1N1)-associated ARDS treated with ECMO and to report incidence, resource utilization, and patient outcomes. DESIGN, SETTING, AND PATIENTS An observational study of all patients (n = 68) with 2009 influenza A(H1N1)-associated ARDS treated with ECMO in 15 intensive care units (ICUs) in Australia and New Zealand between June 1 and August 31, 2009. MAIN OUTCOME MEASURES Incidence, clinical features, degree of pulmonary dysfunction, technical characteristics, duration of ECMO, complications, and survival. RESULTS Sixty-eight patients with severe influenza-associated ARDS were treated with ECMO, of whom 61 had either confirmed 2009 influenza A(H1N1) (n = 53) or influenza A not subtyped (n = 8), representing an incidence rate of 2.6 ECMO cases per million population. An additional 133 patients with influenza A received mechanical ventilation but no ECMO in the same ICUs. The 68 patients who received ECMO had a median (interquartile range [IQR]) age of 34.4 (26.6-43.1) years and 34 patients (50%) were men. Before ECMO, patients had severe respiratory failure despite advanced mechanical ventilatory support with a median (IQR) Pao(2)/fraction of inspired oxygen (Fio(2)) ratio of 56 (48-63), positive end-expiratory pressure of 18 (15-20) cm H(2)O, and an acute lung injury score of 3.8 (3.5-4.0). The median (IQR) duration of ECMO support was 10 (7-15) days. At the time of reporting, 48 of the 68 patients (71%; 95% confidence interval [CI], 60%-82%) had survived to ICU discharge, of whom 32 had survived to hospital discharge and 16 remained as hospital inpatients. Fourteen patients (21%; 95% CI, 11%-30%) had died and 6 remained in the ICU, 2 of whom were still receiving ECMO. CONCLUSIONS During June to August 2009 in Australia and New Zealand, the ICUs at regional referral centers provided mechanical ventilation for many patients with 2009 influenza A(H1N1)-associated respiratory failure, one-third of whom received ECMO. These ECMO-treated patients were often young adults with severe hypoxemia and had a 21% mortality rate at the end of the study period.

Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicentre pharmacokinetic study.

Objectives: In critically ill patients receiving continuous renal replacement therapy, we aimed to assess the variability of antibiotic trough concentrations, the influence of effluent flow rates on such concentrations, and the incidence of suboptimal antibiotic dosage. Design: Prospective, observational, multicenter, pharmacokinetic study. Setting: Four tertiary intensive care units within the multicenter RENAL randomized controlled trial of continuous renal replacement therapy intensity. Patients: Twenty-four critically ill adult patients with acute kidney injury receiving ciprofloxacin, meropenem, piperacillin/tazobactam, or vancomycin during continuous renal replacement therapy. Interventions: We obtained trough blood samples and measured antibiotic concentrations. Measurements and Main Results: We obtained data from 40 dosing intervals and observed wide variability in trough concentrations (6.7-fold for meropenem, 3.8-fold for piperacillin, 10.5-fold for tazobactam, 1.9-fold for vancomycin, and 3.9-fold for ciprofloxacin). The median (interquartile range) trough concentrations (mg/L) for meropenem was 12.1 (7.8–18.4), 105.0 (74.4–204.0)/3.8 (3.4–21.8) for piperacillin/tazobactam, 12.0 (9.8–16.0) for vancomycin, and 3.7 (3.0–5.6) for ciprofloxacin. Overall, 15% of dosing intervals did not meet predetermined minimum therapeutic target concentrations, 40% did not achieve the higher target concentration, and, during 10% of dosing intervals, antibiotic concentrations were excessive. No difference, however, was found between patients on the basis of the intensity of continuous renal replacement therapy; this effect may have been obscured by differences in dosing regimens, time off the filter, or altered pharmacokinetics. Conclusions: There is significant variability in antibiotic trough concentrations in critically ill patients receiving continuous renal replacement therapy, which did not only appear to be influenced by effluent flow rate. Here, empirical dosing of antibiotics failed to achieve the target trough antibiotic concentration during 25% of the dosing intervals.

Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series

BACKGROUND Orthotopic heart transplantation is the gold-standard long-term treatment for medically refractive end-stage heart failure. However, suitable cardiac donors are scarce. Although donation after circulatory death has been used for kidney, liver, and lung transplantation, it is not used for heart transplantation. We report a case series of heart transplantations from donors after circulatory death. METHODS The recipients were patients at St Vincents Hospital, Sydney, Australia. They received Maastricht category III controlled hearts donated after circulatory death from people younger than 40 years and with a maximum warm ischaemic time of 30 min. We retrieved four hearts through initial myocardial protection with supplemented cardioplegia and transferred to an Organ Care System (Transmedics) for preservation, resuscitation, and transportation to the recipient hospital. FINDINGS Three recipients (two men, one woman; mean age 52 years) with low transpulmonary gradients (<8 mm Hg) and without previous cardiac surgery received the transplants. Donor heart warm ischaemic times were 28 min, 25 min, and 22 min, with ex-vivo Organ Care System perfusion times of 257 min, 260 min, and 245 min. Arteriovenous lactate values at the start of perfusion were 8·3-8·1 mmol/L for patient 1, 6·79-6·48 mmol/L for patient 2, and 7·6-7·4 mmol/L for patient 3. End of perfusion lactate values were 3·6-3·6 mmol/L, 2·8-2·3 mmol/L, and 2·69-2·54 mmol/L, respectively, showing favourable lactate uptake. Two patients needed temporary mechanical support. All three recipients had normal cardiac function within a week of transplantation and are making a good recovery at 176, 91, and 77 days after transplantation. INTERPRETATION Strict limitations on donor eligibility, optimised myocardial protection, and use of a portable ex-vivo organ perfusion platform can enable successful, distantly procured orthotopic transplantation of hearts donated after circulatory death. FUNDING NHMRC, John T Reid Charitable Trust, EVOS Trust Fund, Harry Windsor Trust Fund.

Vitamin D deficiency in the intensive care unit: an invisible accomplice to morbidity and mortality?

The association between vitamin D deficiency and chronic illness is well-known. Vitamin D deficiency has been associated with increased mortality in the general population. Despite this knowledge, vitamin D insufficiency is seldom considered and rarely replaced adequately, if at all, in critically ill patients in intensive care. We present a hypothetic model demonstrating how vitamin D deficiency may be an unrecognized contributor to adverse outcome in intensive care patients.

Sedation practice in veno-venous extracorporeal membrane oxygenation: an international survey.

Sedation practice in extracorporeal membrane oxygenation (ECMO) is challenging, and some studies suggest that pharmacokinetics of sedative drugs are altered by the circuitry components. We conducted an international survey of sedation practice in centers offering veno-venous ECMO for adult patients in collaboration with the Extracorporeal Life Support Organization. A total 102 respondents participated representing various experienced centers from around the world. Fifty-eight percent responded that patients on ECMO have a higher or much higher sedation requirement than other critically ill patients, whilst 51% achieved a responsive or cooperative level of sedation. Midazolam (79%), morphine (43%) and fentanyl (45%) were most frequently used. Alpha-2 agonists were prescribed in 66% while propofol was used infrequently (36%). Thirty-five percent did not use continuous muscle relaxants. Responses from experienced users differed to those who reported less experience. Sedation practice in ECMO varies widely. Cooperative or responsive levels of sedation can frequently be achieved, and the drugs used differ from those used in non-ECMO patients.

A randomized study of a single dose of intramuscular cholecalciferol in critically ill adults

Objectives: To determine the effect of two doses of intramuscular cholecalciferol on serial serum 25-hydroxy-vitamin-D levels and on pharmacodynamics endpoints: calcium, phosphate, parathyroid hormone, C-reactive protein, interleukin-6, and cathelicidin in critically ill adults. Design: Prospective randomized interventional study. Setting: Tertiary, academic adult ICU. Patients: Fifty critically ill adults with the systemic inflammatory response syndrome. Intervention: Patients were randomly allocated to receive a single intramuscular dose of either 150,000 IU (0.15 mU) or 300,000 IU (0.3 mU) cholecalciferol. Measurements and Main Results: Pharmacokinetic, pharmacodynamic parameters, and outcome measures were collected over a 14-day period or until ICU discharge, whichever was earlier. Prior to randomization, 28 of 50 patients (56%) were classified as vitamin D deficient. By day 7 after randomization, 15 of 23 (65%) and 14 of 21 patients (67%) normalized vitamin D levels with 0.15 and 0.3 mU, respectively (p = 0.01) and by day 14, 8 of 10 (80%) and 10 of 12 patients (83%) (p = 0.004), respectively. Secondary hyperparathyroidism was manifested in 28% of patients at baseline. Parathyroid hormone levels decreased over the study period with patients achieving vitamin D sufficiency at day 7 having significantly lower parathyroid hormone levels (p < 0.01). Inflammatory markers (C-reactive protein and interleukin-6) fell significantly over the study period. Greater increments in 25-hydroxy-vitamin-D were significantly associated with greater increments in cathelicidin at days 1 and 3 (p = 0.04 and 0.004, respectively). Although in-hospital mortality rate did not differ between the groups, patients who did not mount a parathyroid hormone response to vitamin D deficiency had a higher mortality (35% vs 12%; p = 0.05). No significant adverse effects were observed. Conclusions: A single dose of either dose of intramuscular cholecalciferol corrected vitamin D deficiency in the majority of critically ill patients. Greater vitamin D increments were associated with early greater cathelicidin increases, suggesting a possible mechanism of vitamin D supplementation in inducing bactericidal pleiotropic effects.

Preadmission Bisphosphonate and Mortality in Critically Ill Patients.

CONTEXT Increased bone resorption predicts mortality and bone resorption heightens during critical illness. Bisphosphonates are potent inhibitors of bone resorption. Whether bisphosphonate impacts clinical outcome of intensive care unit (ICU) admission is unknown. OBJECTIVE We investigated the relationship between preadmission bisphosphonate use and clinical outcome in critically ill patients. DESIGN This was a retrospective hospital-based analysis. SETTING The study was conducted at a tertiary referral hospital ICU. PATIENTS A total of 7830 critically ill patients between 2003 and 2014 participated in the study. INTERVENTIONS The intervention included bisphosphonate treatment. MAIN OUTCOME MEASURES In-hospital mortality in the main study (n = 7830) and bone density loss and biochemical and hematological changes in the mechanistic substudy (n = 111) were measured. RESULTS A total of 245 patients received preadmission bisphosphonate. Bisphosphonate users were older (66 ± 16 vs 58 ± 18 y, P < .01) and had greater comorbid disease burden (Charlson comorbidity index: 5.7 ± 3.6 vs 4.6 ± 3.8, P < .01), yet bisphosphonate use was associated with a lower in-hospital mortality (mortality rate ratio: 0.41, 95% confidence interval 0.24-0.71, P < .01), which remained significant after adjusting for age, sex, principal diagnosis, admitting unit, comorbidities and admission year. Bisphosphonate-associated survival benefit was independent of vitamin D, but bisphosphonate/vitamin D co-use was associated with additive reduction in mortality (mortality rate ratio 0.38, 95% confidence interval 0.20-0.71, P < .01). Bone density decreased during ICU admission (-13% ± 19% per week, P < .01) but was significantly attenuated among bisphosphonate users compared with nonusers (-3% ± 13% per week v. -15% ± 14% per week, P < .01), despite similar disease severity on admission. All bisphosphonate users in the substudy survived, whereas six nonusers died. CONCLUSIONS Preadmission bisphosphonate use was associated with superior survival among critically ill patients. Prospective studies examining the effects of bisphosphonate in critical illness are required.

Hypovitaminosis D and morbidity in critical illness: is there proof beyond reasonable doubt?

Vitamin D is recognized to have important actions outside its well-recognized role in musculoskeletal health. These include antimicrobial action, anti-inflammatory, and cardio-protective properties. A high prevalence of vitamin D deficiency and its association with adverse clinical outcomes have now been widely documented in observational studies in the critically ill. These studies of association, however, do not necessarily imply causation, as vitamin D deficiency may be merely a marker of higher illness severity and consequently poorer outcomes. This issue can be clarified only by undertaking high-quality randomized controlled trials of vitamin D supplementation in this vulnerable population.

Blood and Anticoagulation Management in Extracorporeal Membrane Oxygenation for Surgical and Nonsurgical Patients: A Single-Center Retrospective Review

OBJECTIVE To describe blood management and anticoagulation practice for cardiac and respiratory extracorporeal membrane oxygenation (ECMO) with consideration of major surgery at the time of its initiation. DESIGN A single-center retrospective review over 18 months of blood product usage and anticoagulation in patients treated with veno-venous (VV) ECMO versus veno-arterial (VA) ECMO and after major surgery (Sx) versus no surgery (Nsx). SETTING Tertiary metropolitan hospital and state ECMO referral and heart and lung transplantation center. PARTICIPANTS The study comprised 42 patients representing 48 consecutive ECMO runs (16 VV, 32 VA, 26 Sx, 22 Nsx). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Thirty-three percent of the total run time of 362 days was with no continuous infusion of heparin. The mean (standard deviation) daily dose of heparin was lower for Sx versus Nsx patients (11,397 [9,297] v 17,324 [10,387] U, p = 0.047). Sx patients also received more fresh frozen plasma (1.1 [1.93] v 0.2 [0.59] U per day, p = 0.049) and platelets (0.5 [0.51] v 0.1 [0.25] U per day, p = 0.003). VV patients received fewer packed red cells (0.7 [0.45] v 2.0 [2.04] U per day, p = 0.016) and platelets (0.1 [0.18] v 0.4 [0.49] U per day, p = 0.008) compared with VA patients. Survival to hospital discharge was 69%. CONCLUSIONS Heparin doses were low, with frequent interruption of anticoagulation. This was more pronounced in patients with a high bleeding risk recovering from major surgery. The overall usage of blood products was low in VV and Nsx patients, with an overall excellent survival rate.

A retrospective audit of insulin infusion management involving a locally developed dynamic insulin infusion guideline in a tertiary ICU.

BACKGROUND The ideal target blood glucose range for intensive care patients on insulin infusions is controversial. Avoidance of hyperglycaemia and hypoglycaemia are well supported goals. METHODS An audit of insulin infusion management was conducted following the institution of an insulin infusion guideline in a tertiary adult intensive care unit (ICU). The primary aim was to evaluate this guideline for safety and efficacy. Secondary aims were to compare outcomes such as ICU and hospital mortality, rate of severe hypoglycaemia, length of time within target zones, length of stay in ICU and hospital, ventilator hours and use of renal replacement therapy. Data analysis involved descriptive statistical techniques to allow comparison with other reported outcomes. RESULTS Thirty-eight (38) patients were included, representing 137 days of insulin infusions and 2537 blood glucose readings. The mean insulin infusion treatment time was 86.4h (sd ± 86.4), median 48 h (IQR 14.4-141.6). The mean insulin dose per day was 97.6 units (sd ± 115.7), with a median of 68.7 (IQR 38.9-108.3). Blood glucose level (BGL) readings were within the desired target (6-9 mmols/L) and/or the buffer zones (4-6 and 9-12 mmols/L), 92.3% of the time. There were no episodes of severe hypoglycaemia (BGL ≤ 2.2 mmols/L). The median length of ICU stay was 5.9 days. Eighty-four (84) % of the cohort received mechanical ventilation and 26% received renal replacement therapy. The mean ventilation and renal replacement duration were days 6.9 and 9.4 days, respectively. The ICU and hospital mortality was 13.2% and 18.4%, respectively. CONCLUSION The use of this locally developed insulin infusion guideline for hyperglycaemia within this ICU appears safe and effective. When compared to related published randomised controlled trials, the outcomes of this small scale single centre retrospective audit appear congruent. It achieved a severe hypoglycaemic rate of zero, with BGLs within target and buffer zones greater than 90%. It may be worthwhile for intensive care units to consider evaluating their own locally developed insulin infusion guidelines to ensure safety and efficacy.