David Ernest

Distribution of normal saline and 5% albumin infusions in septic patients.

OBJECTIVE To determine the relative distribution of fluid within the extracellular fluid volume (ECFV) after infusing either normal saline or 5% albumin in septic, critically ill patients. DESIGN Prospective, randomized, unblinded, interventional study. SETTING Intensive care unit in a 450-bed, tertiary care, teaching hospital. PATIENTS Septic, critically ill patients (n = 18). INTERVENTIONS Infusion of either normal saline or 5% albumin to a hemodynamic end point determined by the patients clinician. MEASUREMENTS AND MAIN RESULTS Plasma volume (PV), ECFV, cardiac index, and arterial oxygen content were measured immediately before (baseline) and after each fluid infusion. PV and ECFV were measured by dilution of 131I-albumin and 35S sodium sulfate, respectively. Interstitial fluid volume (ISFV) was calculated as ECFV - PV. Baseline values for PV, ISFV, ECFV, and oxygen delivery index did not differ between treatment groups. Infusion of normal saline increased the ECFV by approximately the volume infused, and the expansion of the PV to ISFV was in a ratio of 1:3. Infusion of 5% albumin increased the ECFV by double the volume infused, with both the PV and ISFV expanding by approximately equal amounts. Oxygen delivery index did not increase after either infusion due to the effect of hemodilution. CONCLUSION Expansion of the ECFV in excess of the volume of 5% albumin infused suggests that fluid may move from the intracellular fluid volume to the ECFV in septic patients who receive this fluid.

A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation.

Objectives:To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. Design:Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial. Setting:Two hundred and thirty-three ICUs in 17 countries. Patients:All adult patients admitted with sepsis and suspected disseminated intravascular coagulation as assessed using a modified International Society on Thrombosis and Hemostasis score. Interventions:Patients were randomized to receive IV ART-123 (0.06 mg/kg/d) for 6 days or placebo, in addition to standard of care. The primary endpoint was reduction in mortality. Secondary endpoints included reversal of overt disseminated intravascular coagulation and reduction in disease severity. Measurements and Main Results:A total of 750 patients were randomized, nine of whom did not receive the allocated treatment so that 371 patients received ART-123 and 370 received placebo. There were no meaningful differences between the two groups in any of the baseline variables. Twenty-eight-day mortality was 17.8% in the ART-123 group and 21.6% in the placebo group (Cochran–Mantel–Haenszel two-sided p value of 0.273 in favor of ART-123, which met the predefined statistical test for evidence suggestive of efficacy). There were no statistically significant differences in event-free and alive days between the two groups. d-dimer, prothrombin fragment F1.2 and TATc concentrations were lower in the ART-123 group than in the placebo group. There were no differences between the two groups in organ function, inflammatory markers, bleeding or thrombotic events or in the development of new infections. In post hoc analyses, greatest benefit from ART-123 was seen in patients with at least one organ system dysfunction and an international normalized ratio greater than 1.4 at baseline. Conclusions:ART-123 is a safe intervention in critically ill patients with sepsis and suspected disseminated intravascular coagulation. The study provided evidence suggestive of efficacy supporting further development of this drug in sepsis-associated coagulopathy including disseminated intravascular coagulation. Future study should focus on using ART-123 in the subgroup of patients most likely to respond to this agent.

Distribution of normal saline and 5% albumin infusions in cardiac surgical patients.

Objective To determine the relative distribution of fluid within the extracellular fluid volume (ECFV) and the effect on oxygen delivery after infusing either normal saline or 5% albumin in cardiac surgical patients. Design Prospective, randomized, unblinded, interventional study. Setting Cardiac surgical intensive care unit in a 450-bed teaching hospital. Patients Postoperative cardiac surgical patients (n = 40). Interventions Infusion of either normal saline or 5% albumin to a hemodynamic end point determined by the patient’s clinician. Measurements and Main Results Plasma volume (PV), ECFV, cardiac index, and arterial oxygen content were measured immediately before (baseline) and after each fluid infusion. PV and ECFV were measured by dilution of 131I-albumin and [35S]sodium sulfate, respectively. Interstitial fluid volume (ISFV) was calculated as ECFV − PV. Baseline values for PV, ISFV, ECFV, and oxygen delivery index did not differ between treatment groups. Infusion of normal saline and 5% albumin increased PV by 9 ± 23% and 52 ± 84% of the volume infused, respectively (p < .05), whereas there was no significant difference between saline and albumin in the change in ISFV per volume infused. Only 5% albumin significantly increased cardiac index, although oxygen delivery did not change significantly after either infusion. Conclusions In postoperative cardiac surgical patients, infusion of 5% albumin is approximately five times as efficient as a PV expander but has comparable effects on changes in ISFV and oxygen delivery relative to normal saline.

Heparin-Induced Thrombocytopenia in Medical Surgical Critical Illness

BACKGROUND In a recent multicenter randomized trial comparing unfractionated heparin (UFH) with low-molecular-weight heparin (dalteparin) for thromboprophylaxis in 3,746 critically ill patients, 17 patients (0.5%) developed heparin-induced thrombocytopenia (HIT) based on serotonin-release assay-positive (SRA+) status. A trend to a lower frequency of HIT with dalteparin vs UFH was observed in the intention-to-treat analysis (five vs 12 patients, P = .14), which was statistically significant (three vs 12 patients, P = .046) in a prespecified per-protocol analysis that excluded patients with DVT at study entry. We sought to characterize HIT outcomes and to determine how dalteparin thromboprophylaxis may reduce HIT frequency in patients in the ICU. METHODS In 17 patients with HIT, we analyzed platelet counts and thrombotic events in relation to the study drug and other open-label heparin, to determine whether the study drug plausibly explained seroconversion to SRA+ status and/or breakthrough of thrombocytopenia/thrombosis. We also compared antibody frequencies (dalteparin vs UFH) in 409 patients serologically investigated for HIT. RESULTS HIT-associated thrombosis occurred in 10 of 17 patients (58.8%) (8:1:1 venous:arterial:both). Dalteparin was associated with fewer study drug-attributable HIT-related events (P = .020), including less seroconversion (P = .058) and less breakthrough of thrombocytopenia/thrombosis (P = .032). Antiplatelet factor 4/heparin IgG antibodies by enzyme-linked immunosorbent assay were less frequent among patients receiving dalteparin vs UFH (13.5% vs 27.3%, P < .001). One patient with HIT-associated DVT died after UFH bolus (anaphylactoid reaction), whereas platelet counts recovered in two others with HIT-associated VTE despite continuation of therapeutic-dose UFH. CONCLUSIONS The lower risk of HIT in patients in the ICU receiving dalteparin appears related to both decreased antibody formation and decreased clinical breakthrough of HIT among patients forming antibodies.

Gentamicin clearance during continuous arteriovenous hemodiafiltration.

ObjectiveTo investigate the feasibility of predicting gentamicin dosing requirements during continuous arteriovenous hemodiafiltration (CAVHD). DesignProspective study. SettingGeneral intensive therapy unit in a university teaching hospital. PatientsFive adult patients with acute renal failure in whom both dialytic and gentamicin therapy were indicated. Measurements and Main ResultsCAVHD clearance and total body clearance of gentamicin were estimated from serial gentamicin concentrations in the blood and the combined ultrafiltrate and dialysate. Results (mean ±PT SD) were: CAVHD clearance of gentamicin 5.2 ±PT 1.8 mL/min; total body clearance of gentamicin 20.5 ±PT 6.9 mL/min; ultrafiltrate flow rate 7.0 ±PT 2.4 mL/min (420 ±PT 146 mL/hr). CAVHD clearance of gentamicin was small and represented approximately 25% of total body clearance of gentamicin, although significant interpatient variation existed in these measurements and in the proportion of total gentamicin clearance attributable to CAVHD. CAVHD clearance of gentamicin was related to the ultrafiltrate flow rate (r2 = .81). ConclusionsCAVHD clearance of gentamicin may be predicted for variable ultrafiltrate flow rates. However, due to its minor and variable contribution to total body clearance of gentamicin, prediction of gentamicin dosing requirements based on estimates of CAVHD clearance of gentamicin would be precluded and close monitoring of circulating gentamicin concentrations during CAVHD is necessary. (Crit Care Med 1992; 20:586–589)

A national survey of Australian Intensive Care Unit (ICU) Liaison Nurse (LN) services

BACKGROUND The Intensive Care Unit (ICU) Liaison Nurses (LNs) emerged as a member of the multidisciplinary team to: assist in the transition of patients from ICU to the ward, respond to the deteriorating patient in an appropriate and timely manner, and in some instances act as an integral member of Rapid Response Teams (RRT). PURPOSE To identify the common core aspects and diversity within the ICU LN role across Australia and to determine whether the ICU LN hours of operation and the participation in MET teams has any impact on the activities undertaken by the ICU LN. METHOD This descriptive survey of 152 Australian ICUs was conducted in April 2010. The Advanced Practice Nurse (APN) framework was used to develop the survey instrument, which comprised of four scales, education (5 items), collaboration (6 items), practice (8 items) research and quality (6 items) and a number of demographic questions. Descriptive statistics (mean, standard deviation (SD), median, interquartile ranges (IQR) and frequency) were used to summarise the data. Students t-tests and Pearsons correlations were used to test the hypotheses. RESULTS Surveys were received from 113 hospitals (55 metropolitan, 58 regional): a 74% response rate. ICU LN services operated in 31 (27%) of these hospitals. LN services tended to operate in larger hospitals with higher ICU admission rates. The median weekly hours of operation was 56 (IQR 30; range 7-157), delivered by a median of 1.4 (IQR 0.9; range 0.0-4.2) Full Time Equivalent (FTE) staff. The median weekly patient visits made by the LN was 25 (IQR 44; range 2-145). The LN was reported to be a member of the Medical Emergency Team (MET) in 17 (68%) of the 25 hospitals that provided both MET and ICU LN services. The ICU LN activities were grouped under four key Advanced Practice Nurse (APN) domains: education, collaboration, practice and research/quality. Mean scale scores were calculated for each APN domain. The ICU LN reported being involved in activities associated with all four APN domains, and more frequently they were involved in education and expert practice during their daily work. Neither the presence of a MET nor the weekly operational hours of the LN service significantly affected the key activities undertaken by ICU LNs (education, collaboration, practice, research and quality). CONCLUSION Whilst many hospitals across Australia have introduced an ICU LN service, the staffing, hours of service, job classifications, reporting lines, referral processes and APN activities undertaken by the ICU LN, vary between hospitals, highlighting the diverse nature of ICU LN services across Australia.

Clearance of vancomycin during continuous arteriovenous hemodiafiltration

The clearance of vancomycin during therapy with continuous arteriovenous hemodiafiltration (CAVHD) has been measured in vivo. Vancomycin clearances (n = 16) were 0.636 ± 0.269 L/h (10.5 ± 4.46 ml/min). Effective drug clearances were proportional to ultrafiltrate volumes, reflecting convective clearance. Clearances of vancomycin on CAVHD were approximately twice the values seen with continuous arteriovenous hemofiltration. These data allow construction of a dosing schedule for vancomycin therapy in patients receiving renal support via CAVHD. (Crit Care Med 1990; 18:181)

Alterations in anion gap following cardiopulmonary bypass.

ObjectivesTo evaluate the changes in the anion gap and their relation to hyperlactatemia and alterations in plasma proteins after cardiopulmonary bypass. DesignProspective study. SettingCardiothoracic intensive therapy unit. PatientsOne hundred eleven consecutive patients after cardiopulmonary bypass. Measurements and Main ResultsData were collected before cardiopulmonary bypass and every 6 hrs for 24 hrs after cardiopulmonary bypass. Results were analyzed for the entire cohort and for hyperlactatemic subgroups. The major finding of this study was that the anion gap decreased significantly at all sampling periods relative to precardiopulmonary bypass values, despite the presence of clinically important hyperlactatemia. No correlation between the decrease in plasma protein concentrations and the decrease in anion gap could be demonstrated. ConclusionsThe decrease in anion gap after cardiopulmonary bypass appears to represent a balance between the influences of increased serum chloride and lactate concentrations and reduced plasma protein concentrations. This analysis demonstrates the limitations of the anion gap in the evaluation of a metabolic acidosis after cardiopulmonary bypass. (Crit Care Med 1992; 20:52)

Sibutramine-Associated QT Interval Prolongation and Cardiac Arrest

Objective: To report on a probable association between sibutramine and QT interval prolongation leading to ventricular fibrillation and cardiac arrest. Case Summary: A previously well 51-year-old woman with obesity but no other relevant past medical history or cardiac risk factors was prescribed sibutramine (initial dose 10 mg daily, increased to 15 mg daily after 10wk). Four months after initiation of therapy, the woman developed ventricular fibrillation and was successfully resuscitated. On admission, an electrocardiogram (ECG) demonstrated sinus tachycardia without any ischemic changes and a prolonged QTc interval (545 msec). A subsequent coronary angiogram revealed normal coronary arteries and no other abnormalities. Her QTc interval returned to normal (432 msec) by day 2 and remained within normal limits (<440 msec) thereafter. Due to a favorable neurologic recovery and the absence of any cardiac structural abnormality, the patient was readmitted for implantation of an automatic implantable cardioverter-defibrillator on day 35 and remained well from a cardiac and neurologic standpoint at a 2-year follow-up examination. Discussion: Sibutramine acts centrally to inhibit noradrenaline, dopamine, and serotonin reuptake, thereby sharing similar actions of other QT interval-prolonging drugs. Therefore, sibutramine might be anticipated to also share a tendency to QT interval prolongation. The current prescribing information for sibutramine does not specifically list any precautions or adverse reactions related to QT interval prolongation. QT interval prolongation associated with sibutramine in this case is considered probable based on the Naranjo probability scale. Conclusions: Clinicians prescribing sibutramine should monitor their patients for ECG abnormalities and be cautious in coprescribing drugs known to prolong the QT interval.

Ventilatory failure in shrinking lung syndrome is associated with reduced chest compliance.

Shrinking lung syndrome is an extremely rare feature of systemic lupus erythematosus (SLE). We report on a 49‐year‐old woman with SLE who presented with dyspnoea in type 2 respiratory failure requiring mechanical ventilation. Medical imaging investigations revealed markedly reduced lung volumes and the absence of pulmonary emboli, pulmonary fibrosis or any significant parenchymal infiltrate consistent with shrinking lung syndrome. We observed significantly reduced chest compliance during positive pressure ventilation and noted that this contrasts with a widely held view that diaphragmatic weakness is the major pathophysiological mechanism for ventilatory failure in these patients. She was treated with high‐dose steroids and cyclophosphamide and weaned slowly off full mechanical ventilation. This report highlights an unusual cause of respiratory failure in a patient with SLE and provides support for reduced chest compliance rather than the diaphragmatic weakness as being the significant pathophysiological mechanism for ventilatory failure in these patients.