The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study.

BACKGROUND: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. METHODS: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. RESULTS: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. CONCLUSIONS: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

Severe ketorolac-induced asthma diagnosed by chest computed tomography.

Aspirin-exacerbated respiratory disease (AERD) affects 15% of severe asthmatics and drug reactions cause 200,000 annual deaths in Europe. A 65-year-old lady presented to emergency for progressive abdominal pain. Her medical history included gallstones, asthma, rhinosinusitis and hypertension. She was regularly medicated with inhaled fluticasone, vilanterol and tiotropium, nasal budesonide, pantoprazole, oxazepam and perindopril. She reported partial asthma control and an exacerbation requiring admission to a respiratory ward 6 weeks before. On examination, there was right upper quadrant tenderness and no other changes. Blood tests were normal, and an ultrasound showed gallbladder stones with normal wall. Intravenous ketorolac led to prompt pain resolution. After 30 minutes she became severely dyspnoeic, with an O2 saturation of 85% on high flow O2. She had no breath sounds on the left lung, and there was no wheezing or prolonged expiration. A chest X-ray showed no pneumothorax and a computed tomography (CT) angiography was performed showing bilateral mucoid impaction and sub-segmental atelectasis. Continuous bronchodilation and systemic steroids led to gradual improving in the following 6 hours. After 9 days of admission on a respiratory ward she was discharged home with no symptoms and normal oxygenation. Importantly, she denied previous allergies to nonsteroidal anti-inflammatory drugs (NSAIDs) and had actually taken diclofenac and nimesulid before with no reactions. This report illustrates both an intravenous NSAID causing severe AERD, and how a chest CT may be instrumental for the diagnosis of life-threatening asthma.

Augmented renal clearance in the ICU: results of a multicenter observational study of renal function in critically ill patients with normal plasma creatinine concentrations*.

OBJECTIVE: To describe the prevalence and natural history of augmented renal clearance in a cohort of recently admitted critically ill patients with normal plasma creatinine concentrations. DESIGN: Multicenter, prospective, observational study. SETTING: Four, tertiary-level, university-affiliated, ICUs in Australia, Singapore, Hong Kong, and Portugal. PATIENTS: Study participants had to have an expected ICU length of stay more than 24 hours, no evidence of absolute renal impairment (admission plasma creatinine < 120 µmol/L), and no history of prior renal replacement therapy or chronic kidney disease. Convenience sampling was used at each participating site. INTERVENTIONS: Eight-hour urinary creatinine clearances were collected daily, as the primary method of measuring renal function. Augmented renal clearance was defined by a creatinine clearance more than or equal to 130 mL/min/1.73 m. Additional demographic, physiological, therapeutic, and outcome data were recorded prospectively. MEASUREMENTS AND MAIN RESULTS: Nine hundred thirty-two patients were admitted to the participating ICUs over the study period, and 281 of which were recruited into the study, contributing 1,660 individual creatinine clearance measures. The mean age (95% CI) was 54.4 years (52.5-56.4 yr), Acute Physiology and Chronic Health Evaluation II score was 16 (15.2-16.7), and ICU mortality was 8.5%. Overall, 65.1% manifested augmented renal clearance on at least one occasion during the first seven study days; the majority (74%) of whom did so on more than or equal to 50% of their creatinine clearance measures. Using a mixed-effects model, the presence of augmented renal clearance on study day 1 strongly predicted (p = 0.019) sustained elevation of creatinine clearance in these patients over the first week in ICU. CONCLUSIONS: Augmented renal clearance appears to be a common finding in this patient group, with sustained elevation of creatinine clearance throughout the first week in ICU. Future studies should focus on the implications for accurate dosing of renally eliminated pharmaceuticals in patients with augmented renal clearance, in addition to the potential impact on individual clinical outcomes.

[Catastrophic primary antiphospholipid syndrome]. / Síndroma antifosfolípido primária catastrófica.

Catastrophic antiphospholipid syndrome develops in a minority of patients with antiphospholipid syndrome, and is characterized by acute thrombotic microvasculopathy with multiorganic involvement (three or more organs). The aetiology is unknown, the diagnosis is complex, and the treatment is empiric, mortality may approach 50%. The authors present a clinical case of catastrophic antiphospholipid syndrome, diagnosed in a patient with abdominal pain and severe respiratory failure.