Determination of meropenem in plasma and filtrate-dialysate from patients under continuous veno-venous haemodiafiltration by SPE-LC.

Meropenem, a carbapenem antibiotic displaying a broad spectrum of antibacterial activity, is administered in Medical Intensive Care Unit to critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF). However, there are limited data available to substantial rational dosing decisions in this condition. In an attempt to refine our knowledge and propose a rationally designed dosage regimen, we have developed a HPLC method to determine meropenem after solid-phase extraction (SPE) of plasma and dialysate fluids obtained from patients under CVVHDF. The assay comprises the simultaneous measurement of meropenem's open-ring metabolite UK-1a, whose fate has never been studied in CVVHDF patients. The clean-up procedure involved a SPE on C18 cartridge. Matrix components were eliminated with phosphate buffer pH 7.4 followed by 15:85 MeOH-phosphate buffer pH 7.4. Meropenem and UK-1a were subsequently desorbed with MeOH. The eluates were evaporated under nitrogen at room temperature (RT) and reconstituted in phosphate buffer pH 7.4. Separation was performed at RT on a Nucleosil 100-5 microm C18 AB cartridge column (125 x 4 mm I.D.) equipped with a guard column (8 x 4 mm I.D.) with UV-DAD detection set at 208 nm. The mobile phase was 1 ml min(-1), using a step-wise gradient elution program: %MeOH/0.005 M tetrabutylammonium chloride pH 7.4; 10/90-50/50 in 27 min. Over the range of 5-100 microg ml(-1), the regression coefficient of the calibration curves (plasma and dialysate) were >0.998. The absolute extraction recoveries of meropenem and UK-1a in plasma and filtrate-dialysate were stable and ranged from 88-93 to 72-77% for meropenem, and from 95-104 to 75-82% for UK-1a. In plasma and filtrate-dialysate, respectively, the mean intra-assay precision was 4.1 and 2.6% for meropenem and 4.2 and 3.7% for UK-1a. The inter-assay variability was 2.8 and 3.6% for meropenem and 2.3 and 2.8% for UK-1a. The accuracy was satisfactory for both meropenem and UK-1a with deviation never exceeding 9.0% of the nominal concentrations. The stability of meropenem, studied in biological samples left at RT and at +4 degrees C, was satisfactory with < 5% degradation after 1.5 h in blood but reached 22% in filtrate-dialysate samples stored at RT for 8 h, precluding accurate measurements of meropenem excreted unchanged in the filtrate-dialysate left at RT during the CVVHDF procedure. The method reported here enables accurate measurements of meropenem in critically ill patients under CVVHDF, making dosage individualisation possible in such patients. The levels of the metabolite UK-1a encountered in this population of patients were higher than those observed in healthy volunteers but was similar to those observed in patients with renal impairment under hemodialysis.

Hypercalcaemia and acute renal failure after major burns: An under-diagnosed condition.

BACKGROUND: Hypercalcaemia has been shown to occur in about 20% of patients with major burns requiring prolonged intensive care unit (ICU) treatment, and it may be associated with renal failure. Having observed the early onset of hypercalcaemia, the study aimed to determine the frequency and timing of this condition in a European patient cohort. METHODS: A retrospective cohort study on a prospectively collected, computerised database of the 225 burn-injury ICU admissions between 2001 and 2007 was undertaken. The inclusion criteria included: burns &gt;20% of the body surface area (BSA) or in-hospital stay &gt;20 days. Hypercalcaemia was defined as an ionised plasma calcium (Ca(2+)) concentration &gt;1.32 mmol l(-1) (or total corrected calcium=[Ca]c&gt;2.55 mmol l(-1)). Four emblematic cases are reported in this article. RESULTS: A total of 73 patients met the inclusion criteria (age: 13-88 years, burns: 12-85% BSA): of these, 22 (30%) developed hypercalcaemia. The median time to the first hypercalcaemia value was 21 days. Only 11 patients had both high Ca(2+) and elevated [Ca]c (which remained normal in others). The risk factors of the disorder were burned surface (p=0.017) and immobilisation (fluidised bed use: p&lt;0.05, duration: p=0.02) followed by burned BSA. Acute renal failure tended to be more frequent in hypercalcaemic patients (five (23%) vs. three (6%): p=0.11), while mortality was not increased. The disorder resolved with hydration and mobilisation in most cases: pamidronate was successful in three cases that were most severe. CONCLUSION: Hypercalcaemia and associated acute renal failure occur more frequently and earlier than previously reported. Determining the ionised Ca rather than the total Ca with albumin correction enables earlier detection of hypercalcaemia. Bisphosphonates are an effective treatment option in controlling severe hypercalcaemia and preventing bone loss.

Expérience de dix ans de réanimation chirurgicale d'un centre hospitalier universitaire. Détermination d'un critère d'identification des patients à risque de décéder de coagulopathie irréversible [10 years experience in surgical resuscitation at a university hospital center. Determination of a criterion for identifying patients at risk for fatal irreversible coagulopathy]

The authors evaluated ten years of surgical reanimation in the University Centre of Lausanne (CHUV). Irreversible coagulopathy (IC) is the predominant cause of death for the polytraumatized patient. Acidosis, hypothermy, and coagulation troubles are crucial elements of this coagulopathy. The authors looked for a criterion allowing the identification of dying of IC. In a retrospective study, laboratory results of pH, TP, PTT, thrombocyte count and the need for blood transfusion units were checked for each major step of the primary evaluation and treatment of the polytraumatized patients. These results were considered as critical according to criteria of the literature (30). The authors conclude that the apparation of a third critical value may be useful to identify the polytraumatized patient at risk of dying of IC status. This criterion may also guide the trauma team in selecting a damage control surgical approach (DCS). This criterion was then introduced into an algorithm involving the Emergency Department, the operating room and the Intensive Care Unit. This criterion is a new tool to address the patient at the crucial moment to the appropriate hospital structure.

Initial and Extended Use of Femoral Versus Nonfemoral Double-Lumen Vascular Catheters and Catheter-Related Infection During Continuous Renal Replacement Therapy.

BACKGROUND: The risk of catheter-related infection or bacteremia, with initial and extended use of femoral versus nonfemoral sites for double-lumen vascular catheters (DLVCs) during continuous renal replacement therapy (CRRT), is unclear. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Critically ill patients on CRRT in a combined intensive care unit of a tertiary institution. FACTOR: Femoral versus nonfemoral venous DLVC placement. OUTCOMES: Catheter-related colonization (CRCOL) and bloodstream infection (CRBSI). MEASUREMENTS: CRCOL/CRBSI rates expressed per 1,000 catheter-days. RESULTS: We studied 458 patients (median age, 65 years; 60% males) and 647 DLVCs. Of 405 single-site only DLVC users, 82% versus 18% received exclusively 419 femoral versus 82 jugular or subclavian DLVCs, respectively. The corresponding DLVC indwelling duration was 6±4 versus 7±5 days (P=0.03). Corresponding CRCOL and CRBSI rates (per 1,000 catheter-days) were 9.7 versus 8.8 events (P=0.8) and 1.2 versus 3.5 events (P=0.3), respectively. Overall, 96 patients with extended CRRT received femoral-site insertion first with subsequent site change, including 53 femoral guidewire exchanges, 53 new femoral venipunctures, and 47 new jugular/subclavian sites. CRCOL and CRBSI rates were similar for all such approaches (P=0.7 and P=0.9, respectively). On multivariate analysis, CRCOL risk was higher in patients older than 65 years and weighing >90kg (ORs of 2.1 and 2.2, respectively; P<0.05). This association between higher weight and greater CRCOL risk was significant for femoral DLVCs, but not for nonfemoral sites. Other covariates, including initial or specific DLVC site, guidewire exchange versus new venipuncture, and primary versus secondary DLVC placement, did not significantly affect CRCOL rates. LIMITATIONS: Nonrandomized retrospective design and single-center evaluation. CONCLUSIONS: CRCOL and CRBSI rates in patients on CRRT are low and not influenced significantly by initial or serial femoral catheterizations with guidewire exchange or new venipuncture. CRCOL risk is higher in older and heavier patients, the latter especially so with femoral sites.

How to prescribe nutritional support using computers.

As other intensive care unit (ICU) therapies, nutritional support has become more complex requiring tight supervision and monitoring. It has repeatedly been shown that despite awareness of guidelines and prescription of the recommended amounts of energy (25 kcal/kg), underfeeding remains a prominent problem worldwide. In patients with prolonged stays, overfeeding has also become an issue. This lack of fit between prescription and delivery is largely caused by the lack of visibility of the nutritional results to nurses and clinicians. Computerized systems have brought major improvements, mainly through the customization of nutrition relevant variables in a single place, making them visible. Another important point is the possibility to change the ICU time constant to days and weeks which is the delay relevant for nutritional changes to appear, instead of minutes and hours which are more relevant for critical care.

From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest.

OBJECTIVES: Therapeutic hypothermia has been recommended for postcardiac arrest coma due to ventricular fibrillation. However, no studies have evaluated whether therapeutic hypothermia could be effectively implemented in intensive care practice and whether it would improve the outcome of all comatose patients with cardiac arrest, including those with shock or with cardiac arrest due to nonventricular fibrillation rhythms. DESIGN: Retrospective study. SETTING: Fourteen-bed medical intensive care unit in a university hospital. PATIENTS: Patients were 109 comatose patients with out-of-hospital cardiac arrest due to ventricular fibrillation and nonventricular fibrillation rhythms (asystole/pulseless electrical activity). INTERVENTIONS: We analyzed 55 consecutive patients (June 2002 to December 2004) treated with therapeutic hypothermia (to a central target temperature of 33 degrees C, using external cooling). Fifty-four consecutive patients (June 1999 to May 2002) treated with standard resuscitation served as controls. Efficacy, safety, and outcome at hospital discharge were assessed. Good outcome was defined as Glasgow-Pittsburgh Cerebral Performance category 1 or 2. MEASUREMENTS AND MAIN RESULTS: In patients treated with therapeutic hypothermia, the median time to reach the target temperature was 5 hrs, with a progressive reduction over the 18 months of data collection. Therapeutic hypothermia had a major positive impact on the outcome of patients with cardiac arrest due to ventricular fibrillation (good outcome in 24 of 43 patients [55.8%] of the therapeutic hypothermia group vs. 11 of 43 patients [25.6%] of the standard resuscitation group, p = .004). The benefit of therapeutic hypothermia was also maintained in patients with shock (good outcome in five of 17 patients of the therapeutic hypothermia group vs. zero of 14 of the standard resuscitation group, p = .027). The outcome after cardiac arrest due to nonventricular fibrillation rhythms was poor and did not differ significantly between the two groups. Therapeutic hypothermia was of particular benefit in patients with short duration of cardiac arrest (<30 mins). CONCLUSIONS: Therapeutic hypothermia for the treatment of postcardiac arrest coma can be successfully implemented in intensive care practice with a major benefit on patient outcome, which appeared to be related to the type and the duration of initial cardiac arrest and seemed maintained in patients with shock.

Redistribution of gastric blood flow by embolization of gastric arteries before esophagectomy.

Background. Anastomotic leak remains a common and potentially deleterious complication after esophagectomy. Preoperative embolization of the left gastric artery and splenic artery (PAE) has been suggested to lower anastomotic leak rates. We present the results of our 5-year experience with this technique.Methods. All patients undergoing PAE before esophagectomy since introduction of this technique in 2004 were compared in a 1: 2 matched-pair analysis with patients without PAE. Matching criteria were type of anastomosis, neoadjuvant treatment, comorbidity, and age. Data were derived from a retrospective chart review from 2000 to 2006 that was perpetuated as a prospective database up to date. Outcome measures were anastomotic leak, overall complications, and hospital stay.Results. Between 2000 and 2009, 102 patients underwent esophagectomy for cancer in our institution with an overall leak rate of 19% and a mortality of 8%. All 19 patients having PAE since 2004 were successfully matched 1: 2 to 38 control patients without PAE; both groups were similar regarding demographics and operation characteristics. Two PAE (11%) and 8 control patients (21%) had an anastomotic leak, but the difference was statistically not significant (p = 0.469). Overall and major complication rates for PAE and control group were 89% versus 79% (p = 0.469) and 37% versus 34% (p = 1.000), respectively. Median intensive care unit and hospital stay were 3 versus 3 days (p = 1.000) and 22 versus 17 days (p = 0.321), respectively.Conclusions. In our experience, PAE has no significant impact on complications and anastomotic leak in particular after esophagectomy. (Ann Thorac Surg 2011;91:1556-61) (C) 2011 by The Society of Thoracic Surgeons

Impacto de los errores de medicación en una unidad de curas intensivas y grado de implicación de los profesionales de enfermería

El presente estudio identifica los errores de medicación y valora el grado de notificación de estos errores por parte del personal de enfermería en el Servicio de Medicina Intensiva (SMI), del Hospital Universitario Doctor Josep Trueta.Se realizará un estudio observacional, descriptivo y transversal en el hospital de referencia de las comarcas gerundenses durante el año 2013 y 2014.Los sujetos a estudio serán los profesionales enfermeros y los pacientes ingresados en la unidad. Las variables principales son, por un lado, el error de medicación y por otro la notificación del error.El procedimiento de recogida de datos se basará en proporcionar un cuestionario auto administrado al personal de enfermería, caracterizado por seis preguntas con respuestas cerradas, dos de las cuales tienen la opción de ser abiertas.Para el análisis estadístico se utilizará el programa SPSS. Para la obtención de los resultados se realizará un análisis descriptivo univariante. La variable “error de medicación” se expresará como número de casos y en 1.000 pacientes / día. Las demás variables se presentarán mediante frecuencias

Refractory status epilepticus: A prospective observational study.

Summary Purpose: Status epilepticus (SE) that is resistant to two antiepileptic compounds is defined as refractory status epilepticus (RSE). In the few available retrospective studies, estimated RSE frequency is between 31% and 43% of patients presenting an SE episode; almost all seem to require a coma induction for treatment. We prospectively assessed RSE frequency, clinical predictors, and outcome in a tertiary clinical setting. Methods: Over 2 years we collected 128 consecutives SE episodes (118 patients) in adults. Clinical data and their relationship to outcome (mortality and return to baseline clinical conditions) were analyzed. Results: Twenty-nine of 128 SE episodes (22.6%) were refractory to first- and second-line antiepileptic treatments. Severity of consciousness impairment and de novo episodes were independent predictors of RSE. RSE showed a worse outcome than non-RSE (39% vs. 11% for mortality; 21% vs. 63% for return to baseline clinical conditions). Only 12 patients with RSE (41%) required coma induction for treatment. Discussion: This prospective study identifies clinical factors predicting the onset of SE refractoriness. RSE appears to be less frequent than previously reported in retrospective studies; furthermore, most RSE episodes were treated outside the intensive care unit (ICU). Nonetheless, we confirm that RSE is characterized by high mortality and morbidity.

Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss Transplant Cohort Study.

BACKGROUND: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence. METHODS: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted.

Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Oncohematological patient

Patients with cancer, irrespective of the stage of their disease, can require admission to the intensive care unit as a result of the complications of their underlying process or the surgical or pharmacological treatment provided. The cancer itself, as well as the critical status that can result from the complications of the disease, frequently lead to a high degree of hypermetabolism and inadequate energy intake, causing a high incidence of malnutrition in these patients. Moreover, cancer causes anomalous use of nutritional substrates and therefore the route of administration and proportion and intake of nutrients may differ in these patients from those in noncancer patients.

The neuro-ICU patient and electroencephalography paroxysms: if and when to treat.

PURPOSE OF REVIEW: To review recent clinical data and summarize actual recommendations for the management of electrographic seizures and status epilepticus in neuro-ICU patients. RECENT FINDINGS: Electrographic, 'nonconvulsive', seizures are frequent in neuro-ICU patients including traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage and hypoxic-ischemic encephalopathy. Continuous electroencephalography monitoring is thus of great potential utility. The impact of electrographic seizures on outcome however is not entirely established and it is also unclear what type of electroencephalography paroxysms require treatment and when and how exactly to treat them. Evidence from randomized studies is lacking and will not be available in the near future. Given robust animal and human evidence showing the potential negative impact of seizures on secondary cerebral damage and outcome, treatment of seizures appears reasonable, particularly if related to status epilepticus. On the contrary, over-aggressive antiepileptic therapy entails risks. The management of seizures should therefore be guided individually, based on the underlying cause, the severity of illness and patient comorbidities. SUMMARY: We provide a pragmatic approach for the management of electrographic seizures in neuro-ICU patients. International consensus guidelines on continuous electroencephalography monitoring and seizure therapy are needed and would represent the rationale for a future multicenter randomized trial.

The region makes the difference: disparities in management of acute myocardial infaction within Switzerland

Purpose: To assess geographical differences within Switzerland regarding management and revascularization procedures for acute myocardial infarction (AMI). Methods: Swiss hospital discharge database for period 2007-2008. The main inclusion criterion was AMI as a primary discharge diagnosis. AMI revascularization procedures were identified and seven Swiss regions (Leman, Mittelland, Northwest, Zurich, Central, Eastern and Ticino) were analyzed. Results: Data from 25,674 AMI discharges were analyzed. Almost half (53.6%) of them were managed in a single hospital, the values ranging from 63.1% (Leman) to 31.4% (Ticino) see table. Relative to the total number of discharges, the highest Intensive Care Unit admission rate was in Leman (69.7%), the lowest (16.4%) in Ticino (Swiss average: 35.8%). Intracoronary revascularization rates were highest in Leman (51.6%) and lowest (30.8%) in Central Switzerland (Swiss average: 41.4%). Bare (non-drug-eluting) stents use was highest in Leman (33.1%) and lowest (7.0%) in Ticino (Swiss average: 15.8%), while drug eluting stent use was highest (32.8%) in Ticino and lowest (13.9%) in Central Switzerland (Swiss average: 24.0%). Coronary artery bypass graft rates were highest (4.6%) in Ticino and lowest (0.4%) in Eastern Switzerland (Swiss average: 2.6%). Mechanical circulatory assistance rates were highest (4.1%) in Zurich and lowest (0.4%) in Ticino (Swiss average: 1.7%). The differences in revascularization procedures remained after adjusting for age, single or multiple hospital management and gender. Conclusion: In Switzerland, significant geographical differences in management and revascularization procedures for AMI were found.

Benzodiazepine overtreatment in status epilepticus is related to higher need of intubation and longer hospitalization.

Benzodiazepine (BDZ), a widely recognized first-line status epilepticus (SE) treatment, may lead to respiratory depression. This cohort study investigates the effect of BDZ doses in SE patients in terms of morbidity and mortality. It considers incident SE episodes from a prospective registry (2009-2012), comparing patients receiving standard BDZ dose to those receiving exceeding doses (>30% above recommended dose), in terms of likelihood to receive intubation, morbidity, and mortality. Duration of hospitalization was assessed for subjects needing intubation for airways protection (not for refractory SE treatment) versus matched subjects not admitted to the intensive care unit (ICU). We identified 29 subjects receiving "excessive" and 173 "standard" BDZ dose; 45% of the overtreated patients were intubated for airways protection, but only 8% in the standard-dose group (p < 0.001). However, both groups presented similar clinical outcomes: 50% returned to baseline, 40% acquired a new handicap, and 10% died. Orotracheal intubation due to airways protection was associated with significantly longer hospitalization (mean 2 weeks vs. 1 week, p = 0.008). In conclusion, although administration of excessive BDZ doses in SE treatment does not seem to influence outcome, it is related to higher respiratory depression risk and longer hospitalization, potentially exposing patients to additional complications and costs.

Stress ulcer prophylaxis in non-critically ill patients: a prospective evaluation of the practice in a surgical ward

Introduction The benefit of stress ulcer prophylaxis (SUP) in noncriticallyill patients has not been proved. Over-prescription of SUP isnot devoided of risks (i.e. drug-drug interactions, adverse events).This prospective study aimed to evaluate the use of proton pumpinhibitors (PPIs) for SUP in a visceral surgery ward.Materials & Methods Data collection was performed prospectivelyduring a 8-week period on patients hospitalized in a visceral surgeryward (58 beds). Patients with a PPI prescription for the treatment ofulcers, gastroesophageal reflux disease, esophagitis or epigastralgiawere excluded as well as patients hospitalized twice during the studyperiod. The American Society of Health-System Pharmacists guidelineson SUP were used to assess the appropriateness of de novo PPIprescriptions.Results Among 255 patients in the study, 138 (54.1%) received aprophylaxis with PPI, of which 86 (62.3%) were de novo PPI prescriptions.93.5% of patients received esomeprazole (according to thehospital drug formulary) mainly orally at 40 mg qd. 79.1% of patientshad no risk factors for SUP. 17.9% and 3.0% had one and two riskfactors, respectively. 95% of the patients with PPI were not hospitalizedin the intensive care unit (ICU) before their stay in the visceralsurgery ward. At discharge, PPI therapy was continued in 34.2% ofpatients with a de novo PPI prescription.Discussion & Conclusion This study highlights the over-utilizationof PPIs in non-ICU patients and the inappropriate continuation of PPIprescriptions at discharge. The PPI dosage prescribed for prophylaxiswas probably too high compared with the data of the literature.Treatment recommendations for SUP are needed to restrict PPIuse for justified indications.