Filomena Puntillo

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.

Intrathecal combination of ziconotide and morphine for refractory cancer pain: a rapidly acting and effective choice.

Summary A combination of low doses of ziconotide and morphine, administered intrathecally, allows safe and rapid control of oral opioid–refractory malignant pain. ABSTRACT Ziconotide is a nonopioid intrathecal analgesic drug used to manage moderate to severe chronic pain. The aim of this work is to assess the safety and efficacy of intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral opioids. Patients with malignant pain refractory to high oral opioids doses with a mean visual analogue scale of pain intensity (VASPI) score of ⩾70 mm were enrolled. An IT combination therapy was administered: Ziconotide was started at a dose of 2.4 μg/day, followed by increases of 1.2 μg/day at intervals of at least 7 days, and an initial IT daily dose of morphine was calculated based on its oral daily dose. Percentage change in VASPI scores from baseline was calculated at 2 days, at 7 days, and weekly until the first 28 days. The mean percentage change of VASPI score from baseline was used for efficacy assessment. Safety was monitored based on adverse events and routine laboratory values. Twenty patients were enrolled, with a mean daily VASPI score at rest of 90 ± 7. All had a disseminated cancer with bone metastases involving the spine. The percentage changes in VASPI mean scores from baseline to 2 days, 7 days, and 28 days were 39 ± 13% (95% confidence interval [CI] = 13.61–64.49, P < .001), 51 ± 12% (95% CI = 27.56–74.56, P < .001), and 62 ± 13% (95% CI = 36.03–87.89%, P < .001), respectively. Four patients experienced mild adverse events related to the study drugs. In conclusion, an IT combination of low doses of ziconotide and morphine allows safe and rapid control of oral opioid–refractory malignant pain.

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.

Candida Colonization Index in Patients Admitted to an ICU

Multiple-site colonization with Candida spp. is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At admission (T0) and every three days for two weeks, different samples (pharynx swab, tracheal secretions, stomach contents, etc.) were collected for mycological surveillance. Candida mannan antigen and Candida anti-mannan antibodies were assayed. The Colonization Index (CI) and Corrected Colonization Index were calculated for each time point. Of all patients 70% was already colonized by Candida spp. at T0 and six of them had CI ≥ 0.5. Three patients developed candidemia; they had CI ≥ 0.5 before infection. Positive values of Candida mannan antigen and anti-mannan antibodies were found only in the patients with candidemia. The sensitivity and specificity of the Candida mannan test were 66.6% and 100%, respectively, while the sensitivity and specificity of the anti-mannan antibody test were 100%. In accordance with other authors, we find the surveillance cultures are useful to monitor the Candida colonization in ICU patients. In addition, the sequential observation of anti-mannan antibodies could contribute to early diagnosis of candidiasis more than Candida mannan antigen in immunocompetent patients.

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

Aggression, impulsivity, and suicide risk in benign chronic pain patients - a cross-sectional study

Objectives The objective of this study was to investigate the role that psychopathological dimensions as overt aggression and impulsivity play in determining suicide risk in benign chronic pain patients (CPPs). Furthermore we investigated the possible protective/risk factors which promote these negative feelings, analyzing the relationship between CPPs and their caregivers. Methods We enrolled a total of 208 patients, divided into CPPs and controls affected by internistic diseases. Assessment included collection of sociodemographic and health care data, pain characteristics, administration of visual analog scale (VAS), Modified Overt Aggression Scale (MOAS), Barratt Impulsiveness Scale Version 11 (BIS), Hamilton Depression Rating Scale (HDRS), and a caregiver self-administered questionnaire. All variables were statistically analyzed. Results A significant difference of VAS, MOAS-total/verbal/auto-aggression, HDRS-total/suicide mean scores between the groups were found. BIS mean score was higher in CPPs misusing analgesics. In CPPs a correlation between MOAS-total/verbal/auto-aggression with BIS mean score, MOAS with HDRS-suicide mean score and BIS with HDRS-suicide mean scores were found. The MOAS and BIS mean scores were significantly higher when caregivers were not supportive. Conclusion In CPPs, aggression and impulsivity could increase the risk of suicide. Moreover, impulsivity, overt aggression and pain could be interrelated by a common biological core. Our study supports the importance of a multidisciplinary approach in the CPPs management and the necessity to supervise caregivers, which may become risk/protective factors for the development of feelings interfering with the treatment and rehabilitation of CPPs.

Patient-ventilator interactions in the critically ill

Positive-pressure breaths can be categorized by three variables: the trigger, the limit, and the cycle. They interface the ventilator with the three variables of the breathing pattern: ventilatory drive, ventilatory requirements, and duration and ratio of inspiratory time to total breath cycle duration. The inspiratory effort necessary to trigger a breath is a significant part of the total inspiratory effort; optimization of the triggering mechanisms may improve patient to ventilator interaction. Setting ventilator flow as close as possible to patients flow by appropriate setting of peak value and waveform profile will also improve patient to ventilator interactions. During pressure support ventilation, ineffective efforts and uncoupling between effort and ventilator output are due to the asynchrony between ventilator and patients inspiratory time. They may be counterbalanced by adequate peak flow and flow threshold values. Proportional assist ventilation may optimize patient to ventilator interactions, but continuous monitoring of respiratory mechanics should be performed along with its definitive technologic implementation. Its clinical use should be continuously adapted to resistance and elastance measurements.

A fatal rhino-cerebral zygomycosis in a young woman with latent diabetes mellitus and cerebral blood vessel agenesis.

Rhino-cerebral zygomycosis (RCZ) is an acute rapidly progressive fungal infection usually occurring in patients with diabetes mellitus and ketoacidosis. Patients typically complain of pain located in the facial, nasal or orbital regions, followed by sudden blindness and cranial nerve palsy. Early diagnosis, correction of risk factors, prompt surgical removal and aggressive antifungal therapy are warranted as life-saving treatments. The following report describes a case of a lethal RCZ which occurred in an apparently healthy woman with latent non-decompensated diabetes mellitus and a fetal-type posterior (FTP) circle of Willis.