Haemodynamic effects of parenteral vs. enteral paracetamol in critically ill patients: a randomised controlled trial.

Paracetamol is a commonly used drug in the intensive care unit. There have been reports in the literature of an association with significant hypotension, a potentially important interaction for labile critically ill patients. Route of administration may influence the incidence of hypotension. This single-centre, prospective, open-label, randomised, parallel-arm, active-control trial was designed to determine the incidence of hypotension following the administration of paracetamol to critically ill patients. Fifty adult patients receiving paracetamol for analgesia or pyrexia were randomly assigned to receive either the parenteral or enteral formulation of the drug. Paracetamol concentrations were measured at baseline and at multiple time points over 24 h. The maximal plasma paracetamol concentration was significantly different between routes; 156 vs. 73 micromol.l(-1) [p = 0.0005] following the first dose of parenteral or enteral paracetamol, respectively. Sixteen hypotensive events occurred in 12 patients: parenteral n = 12; enteral n = 4. The incident rate ratio for parenteral vs. enteral paracetamol was 2.94 (95% CI 0.97-8.92; p = 0.06). The incidence of hypotension associated with paracetamol administration is higher than previously reported and tends to be more frequent with parenteral paracetamol.

The rapid and accurate categorisation of critically ill patients (RACE) to identify outcomes of interest for longitudinal studies: a feasibility study.

The capacity to measure the impact of an intervention on long-term functional outcomes might be improved if research methodology reflected our clinical approach, which is to individualise goals of care to what is achievable for each patient. The objective of this multicentre inception cohort study was to evaluate the feasibility of rapidly and accurately categorising patients, who were eligible for simulated enrolment into a clinical trial, into unique categories based on premorbid function. Once a patient met eligibility criteria a rapid 'baseline assessment' was conducted to categorise patients into one of eight specified groups. A subsequent 'gold standard' assessment was made by an independent blinded assessor once patients had recovered sufficiently to allow such an assessment to occur. Accuracy was predefined as agreement in >80% of assessments. One hundred and twenty-two patients received a baseline assessment and 104 (85%) were categorised to a unique category. One hundred and six patients survived to have a gold standard assessment performed, with 100 (94%) assigned to a unique category. Ninety-two patients had both a baseline and gold standard assessment, and these agreed in 65 (71%) patients. It was not feasible to rapidly and accurately categorise patients according to premorbid function.

The effect of augmenting early nutritional energy delivery on quality of life and employment status one year after ICU admission.

Augmenting energy delivery during the acute phase of critical illness may reduce mortality and improve functional outcomes. The objective of this sub-study was to evaluate the effect of early augmented enteral nutrition (EN) during critical illness, on outcomes one year later. We performed prospective longitudinal evaluation of study participants, initially enrolled in The Augmented versus Routine approach to Giving Energy Trial (TARGET), a feasibility study that randomised critically ill patients to 1.5 kcal/ml (augmented) or 1.0 kcal/ml (routine) EN administered at the same rate for up to ten days, who were alive at one year. One year after randomisation Short Form-36 version 2 (SF-36v2) and EuroQol-5D-5L quality of life surveys, and employment status were assessed via telephone survey. At one year there were 71 survivors (1.5 kcal/ml 38 versus 1.0 kcal/ml 33; P=0.55). Thirty-nine (55%) patients consented to this follow-up study and completed the surveys (n = 23 and 16, respectively). The SF-36v2 physical and mental component summary scores were below normal population means but were similar in 1.5 kcal/ml and 1.0 kcal/ml groups (P=0.90 and P=0.71). EuroQol-5D-5L data were also comparable between groups (P=0.70). However, at one-year follow-up, more patients who received 1.5 kcal/ml were employed (7 versus 2; P=0.022). The delivery of 1.5 kcal/ml for a maximum of ten days did not affect self-rated quality of life one year later.

A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators.

PURPOSE: To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. METHODS: Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. RESULTS: From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control: 22.4% [582/2601]; pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity [I(2) = 57%; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0%; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and ICU admission [OR 2.19 (95% CI 1.82-2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I(2) = 71%; P < 0.001) but did not change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07); P = 0.33]. CONCLUSION: EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

An uncommon cause of acute right ventricular failure and high mixed venous oxygen saturation.

Ruptured sinus of Valsalva aneurysms are rare. We report a case in which the usual clinical manifestations were not present and the patient was initially treated as an acute pulmonary embolus. Despite three negative echocardiograms an intra-cardiac shunt was suspected because of a persistently elevated mixed venous oxygen saturation. Cardiac catheterisation confirmed the diagnosis. Surgical repair was performed and post operative recovery was uneventful.

N-acetyl-L-cysteine depresses cardiac performance in patients with septic shock.

OBJECTIVE: To investigate the effects of adjunctive therapy with parenteral N-acetyl-L-cysteine in patients with newly diagnosed septic shock. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Multidisciplinary intensive care unit at a university teaching hospital. PATIENTS: Twenty patients (N-acetyl-L-cysteine group [n = 10], placebo group [n = 10]), 15 male and five female, of mean age 64 +/- 15 (SD) yrs and Acute Physiology and Chronic health Evaluation (APACHE) II score 33 +/- 6, with septic shock within 24 hrs of diagnosis. INTERVENTIONS: After a 2-hr stabilization period (time-zero minus 2 hrs to time-zero), patients received either N-acetyl-L-cysteine in 5% dextrose (150 mg/kg in 100 mL over 15 mins, followed by 50 mg/kg in 250 mL over 4 hrs, and then 100 mg/kg/24 hrs in 500 mL for 44 hrs; N-acetyl-L-cysteine group) or the equivalent volume of 5% dextrose (placebo group). MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport indices were measured at time-zero minus 2 hrs and time-zero, and at multiple time points thereafter until completion of the trial infusion (time-zero plus 48 hrs). A daily Organ Failure Score was recorded for 14 days. Treatment group demographics and hemodynamic variables did not differ significantly between the two groups at time-zero. Mean (SD), pooled mean arterial pressure (MAP), and cardiac index were 75 +/- 15 mm Hg and 3.9 +/- 1.2 L/min/m2, respectively. Over the next 48 hrs, in the N-acetyl-L-cysteine group, there was a progressive decrease, relative to both time-zero and the placebo group, in MAP, cardiac index, and left ventricular stroke work index (p < .01, repeated-measures analysis of variance). Percentage reductions in these values relative to the placebo group at 48 hrs were 23%, 18%, and 43%, respectively Oxygen transport indices, arterial blood gas analyses, Pao2/Fio2 ratio, and shunt did not differ over time between the groups. There was no difference in either daily Organ Failure Score over time (p > .01, repeated-measures analysis of variance) or hospital mortality rate (90% N-acetyl-L-cysteine group, 50% placebo group) (p > .1, logistic regression) between the two groups. CONCLUSION: Adjunctive therapy with N-acetyl-L-cysteine in newly diagnosed septic shock was associated with a depression in cardiovascular performance, as indicated by progressive reductions in cardiac index, left ventricular stroke work index, and MAP.

Ultrasonic assessment of hydronephrosis of pregnancy.

Real-time renal ultrasonographic scans were obtained of 204 subjects, comprising 159 pregnant and 45 control subjects. A classification of hydronephrosis based on calyceal diameters was established, and the overall incidence of hydronephrosis was found to be 90% on the right side and 67% on the left side. Calyceal diameters for both kidneys were found to increase gradually throughout pregnancy, the right more rapidly than the left. Neither parity nor a history of urinary tract problems was found to be relevant to the degree of dilatation.

Parenteral magnesium sulfate versus amiodarone in the therapy of atrial tachyarrhythmias: a prospective, randomized study.

OBJECTIVE: To compare the efficacy of parenteral magnesium sulfate vs. amiodarone in the therapy of atrial tachyarrhythmias in critically ill patients. DESIGN: Prospective, randomized study. SETTING: Multidisciplinary intensive care unit (ICU) at a university teaching hospital. PATIENTS: Forty-two patients, 21 medical and 21 surgical, of mean (SD) age 67 +/- 15 yrs and mean Acute Physiology and Chronic Health Evaluation II score of 22 +/- 6, with atrial tachyarrhythmias (ventricular response rate of > or = 120 beats/min) sustained for > or = 1 hr. INTERVENTIONS: After correction of the plasma potassium concentration to > or = 4.0 mmol/L, patients were randomly allocated to treatment with either a) magnesium sulfate 0.037 g/kg (37 mg/kg) bolus followed by 0.025 g/kg/hr (25 mg/kg/hr); or b) amiodarone 5 mg/kg bolus and 10 mg/kg/24-hr infusion. Therapeutic plasma magnesium concentration in the magnesium sulfate group was 1.4 to 2.0 mmol/L. Therapeutic end point was conversion to sinus rhythm over 24 hrs. MEASUREMENTS AND MAIN RESULTS: At study entry (time 0), initial mean ventricular response rate and systolic blood pressure were 151 +/- 16 (SD) beats/min and 127 +/- 30 mm Hg in the magnesium sulfate group vs. 153 +/- 23 beats/min and 123 +/- 23 mm Hg in the amiodarone group, respectively (p = .8 and .65). Plasma magnesium (time 0) was 0.84 +/- 0.20 vs. 1.02 +/- 0.22 mmol/L in the magnesium and amiodarone group, respectively (p = .1). Eight patients had chronic dysrhythmias (magnesium 3, amiodarone 5). Excluding the two patient deaths (amiodarone group, time 0 + 12 to 24 hrs), no significant change in systolic blood pressure subsequently occurred in either group. In the magnesium group, mean plasma magnesium concentrations were 1.48 +/- 0.36, 1.82 +/- 0.41, 2.16 +/- 0.45, and 1.92 +/- 0.49 mmol/L at time 0 + 1, 4, 12 and 24 hrs, respectively. By logistic regression, the probability of conversion to sinus rhythm was significantly better for magnesium than for amiodarone at time 0 + 4 (0.6 vs. 0.44), 12 (0.72 vs. 0.5), and 24 (0.78 vs. 0.5) hrs. In patients not converting to sinus rhythm, a significant decrease in ventricular response rate occurred at time 0 + to 0.5 hrs (mean decrease 19 beats/min, p = .0001), but there was no specific treatment effect between the magnesium and the amiodarone groups; thereafter, there was no significant reduction in ventricular response rate over time in either group. CONCLUSIONS: Intravenous magnesium sulfate is superior to amiodarone in the conversion of acute atrial tachyarrhythmias, while initial slowing of ventricular response rate in nonconverters appears equally efficacious with both agents.