Walter Verbrugghe

Neurally Adjusted Ventilatory Assist: A Ventilation Tool or a Ventilation Toy?

Mechanical ventilation has, since its introduction into clinical practice, undergone a major evolution from controlled ventilation to various modes of assisted ventilation. Neurally adjusted ventilatory assist (NAVA) is the newest development. The implementation of NAVA requires the introduction of a catheter to measure the electrical activity of the diaphragm (EAdi). NAVA relies, opposite to conventional assisted ventilation modes, on the EAdi to trigger the ventilator breath and to adjust the ventilatory assist to the neural drive. The amplitude of the ventilator assist is determined by the instantaneous EAdi and the NAVA level set by the clinician. The NAVA level amplifies the EAdi signal and determines instantaneous ventilator assist on a breath-to-breath basis. Experimental and clinical data suggest superior patient-ventilator synchrony with NAVA. Patient-ventilator asynchrony is present in 25% of mechanically ventilated patients in the intensive care unit and may contribute to patient discomfort, sleep fragmentation, higher use of sedation, development of delirium, ventilator-induced lung injury, prolonged mechanical ventilation, and ultimately mortality. With NAVA, the reliance on the EAdi signal, together with an intact ventilatory drive and intact breathing reflexes, allows integration of the ventilator in the neuro-ventilatory coupling on a higher level than conventional ventilation modes. The simple monitoring of the EAdi signal alone may provide the clinician with important information to guide ventilator management, especially during the weaning process. Although, until now, little evidence proves the superiority of NAVA on clinically relevant end points, it seems evident that patient populations (eg, COPD and small children) with major patient-ventilator asynchrony may benefit from this new ventilatory tool.

Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients

BackgroundContinuous infusion of vancomycin is increasingly preferred as an alternative to intermittent administration in critically ill patients. Intermittent vancomycin treatment is associated with an increased occurrence of nephrotoxicity. This study was designed to determine the incidence and risk factors of acute kidney injury (AKI) during continuous infusion of vancomycin.MethodsThis was a retrospective, observational, two-center, cohort study in patients with microbiologically documented Gram-positive pneumonia and/or bacteremia and normal baseline renal function. Vancomycin dose was adjusted daily aiming at plateau concentrations of 15-25 μg/mL. AKI was defined as an increase in serum creatinine of 0.3 mg/dL or a 1.5 to 2 times increase from baseline on at least 2 consecutive days after the initiation of vancomycin. Primary data analysis compared patients with AKI with patients who did not develop AKI. A binary logistic regression analysis using the forward stepwise method was used to assess the risk factors associated with AKI.ResultsA total of 129 patients were studied of whom 38 (29.5%) developed AKI. Patients with AKI had higher body weight (77.3 ± 15 vs. 70.5 ± 15.2 kg; p = 0.02), more diabetes (79% vs. 54%; p = 0.01), and a higher vasopressor need (87% vs. 59%; p = 0.002). Serum vancomycin levels, body weight, and SAPS 3 score were identified as variables contributing to AKI. The incidence of AKI increased substantially when treatment duration was prolonged (14.9 ± 9.8 vs. 9.2 ± 4.9 days; p = 0.05) and plasma levels exceeded 30 μg/mL.ConclusionsAKI is frequently observed during continuous vancomycin infusion, particularly when conditions that cause acute (shock) or chronic (diabetes) renal dysfunction are present and vancomycin levels above target range are achieved. Although this study challenges the concept that continuous vancomycin infusion might alleviate the risk of nephrotoxicity in critically ill patients, a direct relationship between vancomycin and nephrotoxicity remains to be proven.

Adverse Drug Events in Intensive Care Units: A Cross-Sectional Study of Prevalence and Risk Factors

BACKGROUND Adverse drug events are considered determinants of patient safety and quality of care. OBJECTIVE To assess the characteristics of adverse drug events in patients admitted to an intensive care unit and determine the impact of severity of illness and nursing workload on the prevalence of the events. METHODS A cross-sectional survey based on retrospective analysis of a high-quality patient data management system for a university-based intensive care unit was used. The prevalence of adverse drug events was measured by using a validated global trigger tool adapted for the critical care environment. Severity was determined by using a validated algorithm. Disease severity and nursing workload were assessed by using validated scoring systems. An investigator blinded to the study and a panel of experts assessed putative serious adverse drug events for each drug taken. Characteristics of patients with and without adverse drug events were compared by using univariate and stepwise multivariate logistic regression. RESULTS During 175 of 1009 intensive care unit days screened, 230 adverse drug events occurred in 79 patients. The most common events were hypoglycemia, prolonged activated partial thromboplastin time, and hypokalemia. Of the adverse events, 96% were classified as causing temporary harm and 4% as causing complications. Both mean severity of disease and nursing workload were significantly higher on days when 1 or more adverse drug events occurred. CONCLUSION Adverse drug events were common in intensive care unit patients and were associated with illness severity and nursing workload.

A retrospective observational study on the efficacy of colistin by inhalation as compared to parenteral administration for the treatment of nosocomial pneumonia associated with multidrug-resistant Pseudomonas aeruginosa

BackgroundColistin is used as last treatment option for pneumonia associated with multidrug-resistant (MDR) Pseudomonas spp.. Literature about the best administration mode (inhalation versus parenteral treatment) is lacking.MethodsA retrospective study of 20 intensive care patients with a pneumonia associated with MDR P. aeruginosa receiving colistin sulphomethate sodium (Colistineb®) between 2007 and 2009 was performed. A strain was considered multidrug-resistant if it was resistant to at least 6 of the following antibiotics: piperacillin-tazobactam, ceftazidime, cefepime, meropenem, aztreonam, ciprofloxacin, and amikacin. The administration mode, predicted mortality based on the SAPS3 score, SOFA score at onset of the colistin treatment, clinical and microbiological response, and mortality during the episode of the infection were analysed. The non parametric Kruskal-Wallis and Fishers Exact test were used for statistical analysis of respectively the predicted mortality/SOFA score and mortality rate.ResultsSix patients received colistin by inhalation only, 5 were treated only parenterally, and 9 by a combination of both administration modes. All patients received concomitant beta-lactam therapy. The mean predicted mortalities were respectively 72%, 68%, and 69% (p = 0.91). SOFA scores at the onset of the treatment were also comparable (p = 0.87). Clinical response was favorable in all patients receiving colistin by inhalation (6/6) and in 40% (2/5) of the patients receiving colistin parenterally (p = 0.06). In the patients with colistin administered both via inhalation and parenterally, clinical response was favorable in 78% of the patients (7/9) (p = 0.27 as compared to the treatment group receiving colistin only parenterally). When all patients with inhalation therapy were compared to the group without inhalation therapy, a favorable clinical response was present in respectively 87% and 40% (p = 0.06). In none of the patients, the Pseudomonas spp. was eradicated from the follow-up cultures.All patients in the parenterally treated group died. None of the patients receiving colistin by inhalation, and 3 of 9 patients of the combination group eventually died (p = 0.002 and p = 0.03 respectively as compared to the group receiving colistin only parenterally).ConclusionsAerosolized colistin could be beneficial as adjunctive treatment for the management of pneumonia due to MDR P. aeruginosa.

Continuous infusion of antibiotics in the critically ill: The new holy grail for beta-lactams and vancomycin?

The alarming global rise of antimicrobial resistance combined with the lack of new antimicrobial agents has led to a renewed interest in optimization of our current antibiotics. Continuous infusion (CI) of time-dependent antibiotics has certain theoretical advantages toward efficacy based on pharmacokinetic/pharmacodynamic principles. We reviewed the available clinical studies concerning continuous infusion of beta-lactam antibiotics and vancomycin in critically ill patients. We conclude that CI of beta-lactam antibiotics is not necessarily more advantageous for all patients. Continuous infusion is only likely to have clinical benefits in subpopulations of patients where intermittent infusion is unable to achieve an adequate time above the minimal inhibitory concentration (T > MIC). For example, in patients with infections caused by organisms with elevated MICs, patients with altered pharmacokinetics (such as the critically ill) and possibly also immunocompromised patients. For vancomycin CI can be chosen, not always for better clinical efficacy, but because it is practical, cheaper, associated with less AUC24h (area under the curve >24 h)-variability, and easier to monitor.

Considerable exposure to the endocrine disrupting chemicals phthalates and bisphenol-A in intensive care unit (ICU) patients.

Critical care medicine has largely benefited from plastic-containing medical devices. However, bisphenol-A (BPA) and phthalates present in the plastics can leach from such devices. We hypothesized that intensive care unit (ICU) patients are exposed to BPA and phthalates through (plastic) medical devices. Serum (n = 118) and urine (n= 102) samples of adult ICU patients (n = 35) were analyzed for total BPA and phthalate metabolites (PMs). Our results showed that adult ICU patients are continuously exposed to phthalates, such as di(2-ethylhexyl)phthalate (DEHP), as well as to BPA, albeit to a lesser extent. This exposure resulted in detectable high serum and urinary levels in almost every patient and at every studied time point. Moreover, these levels were significantly higher than in controls or compared to referenced literature. The chronology of exposure was demonstrated: pre-operative urinary and serum levels of the DEHP metabolites were often below the detection limit. Plastic-containing medical devices were the main source of DEHP exposure: post-operative patients on hemofiltration, extracorporeal membrane oxygenation or both showed serum levels 100-or 1000-fold higher than the levels in the general population reported in the literature. The serum and some of the urinary levels of the DEHP metabolites are the highest ever reported in humans; some at biologically highly relevant concentrations of ≥ 10-50 μM. Despite the continuously tightening regulations, BPA and DEHP appear to be still present in (some) medical devices. Because patient safety is a concern in the ICU, further research into the (possibly toxic and clinical) effects of these chemicals released from medical devices is imperiously necessary.

Two unusual pediatric cases of dilutional hyponatremia.

Dilutional hyponatremia, although not uncommon, is an underestimated problem in the pediatric population. In most cases, it results from excessive hydration or water retention, also described as the so-called water intoxication. One of the most known causes is the use of desmopressin in enuretic children. This drug enhances the free water reabsorption in the renal collecting ducts. The addition of the anticholinergic agent oxybutynin aggravated the condition by causing a dry mouth with excessive thirst and water intake in our first case. Dietary water overconsumption, either voluntary or involuntary, is a phenomenon seen in formula-fed babies. But in our second case, a game involving forced ingestion of large amounts of water had serious consequences including hyponatremia-related coma. An effort should therefore be made to inform caretakers about the risks of these games. These cases, provoked by rather unusual and peculiar causes, illustrate again that electrolytes and especially serum [Na+] are key points to be determined in a child with diminished consciousness. Moreover, an accurate history including the intake of medication and dietary information should be made.

Is acyclovir effective among critically ill patients with herpes simplex in the respiratory tract

BACKGROUND AND OBJECTIVE The relevance of the detection of herpes simplex virus type 1 (HSV-1) in the respiratory tract of patients in the intensive care unit (ICU) is unclear. Therefore, it is uncertain whether treatment with an antiviral agent could be beneficial for these patients. STUDY DESIGN We retrospectively reviewed the records of ICU patients with a positive HSV-1 culture in the respiratory tract or bronchoalveolar lavage (BAL) fluid. We evaluated whether acyclovir treatment (n=106) could have a beneficial effect on mortality as compared with the standard treatment (n=106). RESULTS Acyclovir treatment was positively linked to in-hospital and ICU-mortality reduction. This favourable influence remained present after correcting for possible confounders and using propensity-adjusted and propensity-matched cohorts: with an odds ratio in the treated group of 3.19 (95% CI 1.79-5.69, p=0.001) for ICU survival and of 3.55 (95% CI 2.16-5.85, p<0.001) for in-hospital survival. The subgroup with HSV-1 detected in the BAL-fluid is the sole contributor to this difference. In the BAL-fluid detected group, 48% (n=10) of non-treated patients died in the ICU, versus 21% (n=6) in the acyclovir-treated group (p=0.033), occurring despite an even longer duration of ventilation or ICU stay. CONCLUSIONS These data highlight the hypothesis that it might be worthwhile to consider treatment of HSV-1 in ICU patients depending on the type of respiratory sample in which the virus is detected. These results warrant a prospective trial to prove causality.

Effect of isotonic versus hypotonic maintenance fluid therapy on urine output, fluid balance, and electrolyte homeostasis: a crossover study in fasting adult volunteers

Abstract Background. Daily and globally, millions of adult hospitalized patients are exposed to maintenance i.v. fluid solutions supported by limited scientific evidence. In particular, it remains unclear whether fluid tonicity contributes to the recently established detrimental effects of fluid, sodium, and chloride overload. Methods. This crossover study consisted of two 48 h study periods, during which 12 fasting healthy adults were treated with a frequently prescribed solution (NaCl 0.9% in glucose 5% supplemented by 40 mmol litre−1 of potassium chloride) and a premixed hypotonic fluid (NaCl 0.32% in glucose 5% containing 26 mmol litre−1 of potassium) at a daily rate of 25 ml kg−1 of body weight. The primary end point was cumulative urine volume; fluid balance was thus calculated. We also explored the physiological mechanisms behind our findings and assessed electrolyte concentrations. Results. After 48 h, 595 ml (95% CI: 454–735) less urine was voided with isotonic fluids than hypotonic fluids (P<0.001), or 803 ml (95% CI: 692–915) after excluding an outlier with ‘exaggerated natriuresis of hypertension’. The isotonic treatment was characterized by a significant decrease in aldosterone (P<0.001). Sodium concentrations were higher in the isotonic arm (P<0.001), but all measurements remained within the normal range. Potassium concentrations did not differ between the two solutions (P=0.45). Chloride concentrations were higher with the isotonic treatment (P<0.001), even causing hyperchloraemia. Conclusions. Even at maintenance rate, isotonic solutions caused lower urine output, characterized by decreased aldosterone concentrations indicating (unintentional) volume expansion, than hypotonic solutions and were associated with hyperchloraemia. Despite their lower sodium and potassium content, hypotonic fluids were not associated with hyponatraemia or hypokalaemia. Clinical trial registration. ClinicalTrials.gov (NCT02822898) and EudraCT (2016-001846-24).

The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial

BACKGROUND Whether antibiotic rotation strategies reduce prevalence of antibiotic-resistant, Gram-negative bacteria in intensive care units (ICUs) has not been accurately established. We aimed to assess whether cycling of antibiotics compared with a mixing strategy (changing antibiotic to an alternative class for each consecutive patient) would reduce the prevalence of antibiotic-resistant, Gram-negative bacteria in European intensive care units (ICUs). METHODS In a cluster-randomised crossover study, we randomly assigned ICUs to use one of three antibiotic groups (third-generation or fourth-generation cephalosporins, piperacillin-tazobactam, and carbapenems) as preferred empirical treatment during 6-week periods (cycling) or to change preference after every consecutively treated patient (mixing). Computer-based randomisation of intervention and rotated antibiotic sequence was done centrally. Cycling or mixing was applied for 9 months; then, following a washout period, the alternative strategy was implemented. We defined antibiotic-resistant, Gram-negative bacteria as Enterobacteriaceae with extended-spectrum β-lactamase production or piperacillin-tazobactam resistance, and Acinetobacter spp and Pseudomonas aeruginosa with piperacillin-tazobactam or carbapenem resistance. Data were collected for all admissions during the study. The primary endpoint was average, unit-wide, monthly point prevalence of antibiotic-resistant, Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders. This trial is registered with ClinicalTrials.gov, number NCT01293071. FINDINGS Eight ICUs (from Belgium, France, Germany, Portugal, and Slovenia) were randomly assigned and patients enrolled from June 27, 2011, to Feb 16, 2014. 4069 patients were admitted during the cycling periods in total and 4707 were admitted during the mixing periods. Of these, 745 patients during cycling and 853 patients during mixing were present during the monthly point-prevalence surveys, and were included in the main analysis. Mean prevalence of the composite primary endpoint was 23% (168/745) during cycling and 22% (184/853) during mixing (p=0·64), yielding an adjusted incidence rate ratio during mixing of 1·039 (95% CI 0·837-1·291; p=0·73). There was no difference in all-cause in-ICU mortality between intervention periods. INTERPRETATION Antibiotic cycling does not reduce the prevalence of carriage of antibiotic-resistant, Gram-negative bacteria in patients admitted to the ICU. FUNDING European Union Seventh Framework Programme.