Lidia Dalfino

High Dose, Extended-Interval Colistin Administration in Critically Ill Patients: Is this the Right Dosing Strategy? A Preliminary Study

In critically ill patients with otherwise untreatable nosocomial infection due to gram-negative bacteria susceptible only to colistin, a high-dose, extended-interval colistin dosing regimen is, according to the pharmacokinetic/pharmacodynamic behavior of the drug, associated with low renal toxicity and high efficacy.

Haemodynamic goal-directed therapy and postoperative infections: earlier is better. a systematic review and meta-analysis

IntroductionInfectious complications are the main causes of postoperative morbidity. The early timing of their promoting factors is the rationale for perioperative strategies attempting to reduce them. Our aim was to determine the effects of perioperative haemodynamic goal-directed therapy on postoperative infection rates.MethodsWe performed a systematic review and meta-analysis. MEDLINE, EMBASE, The Cochrane Library and the DARE databases were searched up to March 2011. Randomised, controlled trials of major surgery in adult patients managed with perioperative goal-directed therapy or according to routine haemodynamic practice were included. Primary outcome measure was specific type of infection.ResultsTwenty-six randomised, controlled trials with a combined total of 4,188 participants met our inclusion criteria. Perioperative goal-directed therapy significantly reduced surgical site infections (pooled OR 0.58, 95% CI 0.46 to 0.74; P < 0.0001), pneumonia (pooled OR 0.71, 95% CI 0.55 to 0.92; P = 0.009), and urinary tract infections (pooled OR 0.44, 95% CI 0.22 to 0.84; P = 0.02). A significant benefit was found regarding total infectious episodes (OR 0.40, 95% CI 0.28 to 0.58; P < 0.00001).ConclusionsFlow-directed haemodynamic therapy designed to optimise oxygen delivery protects surgical patients against postoperative hospital-acquired infections and must be strongly encouraged, particularly in the high-risk surgical population.

A comparison between fenoldopam and low-dose dopamine in early renal dysfunction of critically ill patients*

Objective:Fenoldopam mesylate is a selective dopamine-1 agonist, with no effect on dopamine-2 and &agr;1 receptors, producing a selective renal vasodilation. This may favor the kidney oxygen supply/demand ratio and prevent acute renal failure. The aim of the study was to investigate if fenoldopam can provide greater benefit than low-dose dopamine in early renal dysfunction of critically ill patients. Design:Prospective, multiple-center, randomized, controlled trial. Setting:University and city hospital intensive care units. Patients:One hundred adult critically ill patients with early renal dysfunction (intensive care unit stay <1 wk, hemodynamic stability, and urine output ≤0.5 mL/kg over a 6-hr period and/or serum creatinine concentration ≥1.5 mg/dL and ≤ 3.5 mg/dL). Interventions:Patients were randomized to receive 2 &mgr;g/kg/min dopamine (group D) or 0.1 &mgr;g/kg/min fenoldopam mesylate (group F). Drugs were administered as continuous infusion over a 4-day period. Measurements and Main Results:Systemic hemodynamic and renal function variables were recorded daily. The two groups were well matched at enrollment for illness severity and hemodynamic and renal dysfunction. No differences in heart rate or systolic, diastolic, or mean arterial pressure were observed between groups. Fenoldopam produced a more significant reduction in creatinine values compared with dopamine after 2, 3, and 4 days of infusion (change from baseline at time 2, −0.32 vs. −0.03 mg/dL, p = .047; at time 3, −0.45 vs. −0.09 mg/dL, p = .047; and at time 4, −.041 vs. −0.09 mg/dL, p = .02, in groups F and D, respectively). The maximum decrease in creatinine compared with baseline was significantly greater in group F than group D (−0.53 ± 0.47 vs. −0.34 ± 0.38 mg/dL, p = .027). Moreover, 66% of patients in group F had a creatinine decrease >10% of the baseline value at the end of infusion, compared with only 46% in dopamine group (chi-square = 4.06, p = .04). Total urinary output during drug infusion was not significantly different between groups. After 1 day, urinary output was lower in group F compared with group D (p < .05). Conclusions:In critically ill patients, a continuous infusion of fenoldopam at 0.1 &mgr;g/kg/min does not cause any clinically significant hemodynamic impairment and improves renal function compared with renal dose dopamine. In the setting of acute early renal dysfunction, before severe renal failure has occurred, the attempt to reverse renal hypoperfusion with fenoldopam is more effective than with low-dose dopamine.

Use of N-terminal pro-brain natriuretic peptide to detect acute cardiac dysfunction during weaning failure in difficult-to-wean patients with chronic obstructive pulmonary disease.

Objective: To evaluate the utility of serial measurements of plasma N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) to detect acute cardiac dysfunction during weaning failure in difficult to wean patients with chronic obstructive pulmonary disease. Design: Prospective observational cohort study. Setting: A 14‐bed general intensive care unit in a university hospital. Patients: Nineteen patients mechanically ventilated for chronic obstructive pulmonary disease exacerbation who were difficult to wean. Interventions: None. Measurements and Main Results: Cardiac and hemodynamic variables, arterial and central venous blood gas, breathing pattern, respiratory mechanics, indexes of oxygen cost of breathing, and plasma levels of NT‐proBNP were measured and analyzed immediately before (baseline) and at the end of a spontaneous breathing trial. Eight of 19 patients (42%) were identified with acute cardiac dysfunction at the end of the weaning trial. Baseline NT‐proBNP levels were significantly higher (median 5000, interquartile range 4218 pg/mL) in these patients than in patients without evidence of acute cardiac dysfunction (median 1705, interquartile range 3491 pg/mL). Plasma levels of NT‐proBNP increased significantly at the end of the spontaneous breathing trial only in patients with acute cardiac dysfunction (median 12,733, interquartile range 16,456 pg/mL, p < .05). The elevation in NT‐proBNP at the end of the weaning trial had a good diagnostic performance in detecting acute cardiac dysfunction, as estimated by area under the receiver operating characteristic curve analysis (area under the curve 0.909, se 0.077, 95% confidence interval 0.69–0.98; p < .0001, cutoff = 184.7 pg/mL). Conclusions: Serial measurements of NT‐proBNP plasma levels provided a noninvasive manner to detect acute cardiac dysfunction during an unsuccessful weaning trial in difficult to wean patients with chronic obstructive pulmonary disease. The utility of this test as a complement of the standard clinical monitoring of the weaning trial deserves further investigation.

Haemodynamic goal-directed therapy in cardiac and vascular surgery. A systematic review and meta-analysis

In cardiovascular surgery, reduced organ perfusion and oxygen delivery contribute to increased postoperative morbidity and prolonged intensive care unit stay. Goal-directed therapy (GDT), a perioperative haemodynamic strategy aiming to increase cardiac output, is helpful in preventing postoperative complications, but studies in the context of cardiovascular surgery have produced conflicting results. The purpose of the present meta-analysis is to determine the effects of perioperative haemodynamic goal-directed therapy on mortality and morbidity in cardiac and vascular surgery. MEDLINE, EMBASE, The Cochrane Library and the DARE databases were searched until July 2011. Randomized controlled trials reporting on adult cardiac or vascular surgical patients managed with perioperative GDT or according to routine haemodynamic practice were included. Primary outcome measures were mortality and morbidity. Data synthesis was obtained by using odds ratio (OR) with 95% confidence interval (CI) by a random effects model. An OR <1 favoured GDT. Statistical heterogeneity was assessed by Q and I(2) statistics. Eleven articles (five cardiac surgery and six vascular procedures), enrolling a total sample of 1179 patients, were included in the analysis. As compared with routine haemodynamic practice, perioperative GDT did not reduce mortality in either cardiac or vascular surgery (pooled OR 0.87; 95% CI 0.37-2.02; statistical power 64%). GDT significantly reduced the number of cardiac patients with complications (OR 0.34; 95% CI 0.18-0.63; P = 0.0006), but no effect was observed in vascular patients (OR, 0.84; 95% CI 0.45-1.56; P = 0.58). Perioperative GDT prevents postoperative complications in cardiac surgery patients, while it has no effect in vascular surgery. The different characteristics and comorbidities of the population enrolled could explain these conflicting results. More trials conforming to the characteristics of low-risk-of-bias studies and enrolling a larger and well-defined population of patients are needed to better clarify the effect of GDT in the specific setting of cardiovascular surgery.

Colistin-associated Acute Kidney Injury in Severely Ill Patients: A Step Toward a Better Renal Care? A Prospective Cohort Study

BACKGROUND Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy. METHODS A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD)-based dosing approach. RESULTS Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87-11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9-9.2; P < .001) and age (1.03; 1.0-1.05; P = .028), whereas a strong independent renal-protective role emerged for ascorbic acid (0.27; .12-.57; P < .001). CONCLUSIONS In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin.

Simultaneous Occurrence of Ipsilateral Cluster Headache and Chronic Paroxysmal Hemicrania: A Case Report

A 42‐year‐old man came to our headache unit in October 1995 complaining of recurrent attacks of headache, which had begun in February 1991. Chronic cluster headache was diagnosed, and he was given verapamil, 360 mg per day. The attacks ceased in the following months and verapamil was stopped in March 1996. In May 1997, a recurrence of the attacks required the readministration of verapamil, 360 mg per day. The attacks decreased (one to three per week), but after 2 months the patient reported a worsening in his condition due to the appearance of shorter attacks, which were diagnosed as chronic paroxysmal hemicrania. The administration of indomethacin, 225 mg per day, resulted in the disappearance of the short attacks.

Oral nystatin prophylaxis in surgical/trauma ICU patients: a randomised clinical trial

IntroductionCandida prophylaxis in ICU is still a matter of debate. Oral chemoprophylaxis has been advocated to reduce the incidence of Candida colonisation and infection.MethodsWe performed a randomised trial studying a single drug (nystatin) versus control in surgical/trauma ICU patients. Multiple-site testing for fungi was performed in each patient on ICU admission (T0) and subsequently every 3 days (T3, T6, T9, and so forth). The primary evaluation criterion was the time course of the corrected colonisation index.ResultsNinety-nine patients were enrolled. At admission, 69 patients exhibited Candida colonisation: the most frequently colonised body sites were the stomach and the pharynx. The most frequent isolated species was Candida albicans. The corrected colonisation index was similar in the two groups at T0 (P = 0.36), while a significant statistical difference was observed between the treatment and control groups at T6 (median 0.14 and 0.33, respectively; P = 0.0016), at T9 (median 0.00 and 0.28, respectively; P = 0.0001), at T12 (median 0.00 and 0.41, respectively; P = 0.0008), and at T15 (median 0.00 and 0.42, respectively; P < 0.0003). The same results were obtained in the subgroup of patients already colonised at ICU admission.ConclusionThis trial shows that nystatin prophylaxis significantly reduces fungal colonisation in surgical/trauma ICU patients, even if already colonised.Trial registrationClinicalTrials.gov: NCT01495039

Protocoled resuscitation and the prevention of acute kidney injury

Purpose of reviewAcute kidney injury (AKI) occurrence in critically ill patients is common and is associated with a substantial increase in morbidity and mortality. The scope of this review is to summarize the most recent evidence-based knowledge for prevention of AKI. Recent findingsRecent recommendations for prevention of AKI in ICU patients are all ‘negative’ and, similarly, the most recent and updated guidelines about major topic areas of interest for AKI, including definition and classification, prevention, and pharmacologic treatment, have failed to identify single evidence-based recommendations for prevention and treatment of AKI. Therefore, the evaluation and management of AKI should be guided by clinical algorithms aiming to protocolized hemodynamic optimization, metabolic control, monitoring of intra-abdominal hypertension, use of diuretics to control fluid overload, and careful management of nephrotoxic factors. SummaryKey components of optimal AKI prevention include maintenance of renal perfusion and avoidance of precipitating factors. Adequate renal blood flow maintenance is the first strategy to employ not only to assure renal oxygenation, but also to prevent nephrotoxic drugs-associated AKI. Many potential therapies and interventions are on the horizon, but most of the future research will need to focus more on a step-wise, protocoled, kidney-oriented approach, than on single treatments.

Intra-abdominal hypertension in cardiac surgery

OBJECTIVES The occurrence of intra-abdominal hypertension (IAH), as well as its promoting factors in cardiac surgery, has been poorly explored. The aim of the present study was to characterize intra-abdominal pressure (IAP) variations in patients undergoing cardiac surgical procedures, and to identify the risk factors for IAH in this setting. METHODS All consecutive adult patients requiring postoperative intensive care unit admission for >24 h were enrolled. Demographic data, pre-existing comorbidities, type and duration of surgery, cardiopulmonary bypass (CPB) use and duration, perioperative IAP, organ function and fluid balance were recorded. IAH was defined as a sustained increase in IAP >12 mmHg. Multivariate logistic regression and stepwise analyses identified the baseline and perioperative variables associated with IAH. RESULTS Of 69 patients, 22 (31.8%) developed IAH. In the logistic model, baseline IAP, high central venous pressure, vasoactive drugs administration, positive fluid balance, AKI, CPB, total sequential organ failure assessment score and age were all promoting factors for IAH (Hosmer-Lemeshow χ(2) = 7.23; P = 0.843). Baseline IAP, high central venous pressure and positive fluid balance were independent risk factors for IAH in the stepwise analysis. The ROC curve analysis, obtained by plotting the occurrence of IAH vs the IAP baseline value, showed an AUC of 0.75 (SE 0.064; 99% CI 0.62-0.87; P < 0.0001). The best IAP cut-off value was at 8 mmHg (sensitivity 63% and specificity 76%). Considering on- and off-pump surgery groups, fluid balance and vasoactive drugs use were significantly higher in the on-pump group. Linear regression analysis showed a positive correlation (P = 0.0001) between IAP changes and fluid balance only in the on-pump group. CONCLUSIONS IAH develops in one-third of cardiac surgery patients and is strongly associated with higher baseline IAP values, higher central venous pressure, positive fluid balance, extracorporeal circulation, use of vasoactive drugs and AKI. Determinants of IAH should be accurately assessed before and after surgery, and patients presenting risk factors must be monitored properly during the perioperative period. In this context, the baseline value of IAP may be a valuable and early warning parameter for IAH occurrence.