Rodrigo Cavallazzi

Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature.

Objectives:A systematic review of the literature to determine the ability of dynamic changes in arterial waveform-derived variables to predict fluid responsiveness and compare these with static indices of fluid responsiveness. The assessment of a patients intravascular volume is one of the most difficult tasks in critical care medicine. Conventional static hemodynamic variables have proven unreliable as predictors of volume responsiveness. Dynamic changes in systolic pressure, pulse pressure, and stroke volume in patients undergoing mechanical ventilation have emerged as useful techniques to assess volume responsiveness. Data Sources:MEDLINE, EMBASE, Cochrane Register of Controlled Trials and citation review of relevant primary and review articles. Study Selection:Clinical studies that evaluated the association between stroke volume variation, pulse pressure variation, and/or stroke volume variation and the change in stroke volume/cardiac index after a fluid or positive end-expiratory pressure challenge. Data Extraction and Synthesis:Data were abstracted on study design, study size, study setting, patient population, and the correlation coefficient and/or receiver operating characteristic between the baseline systolic pressure variation, stroke volume variation, and/or pulse pressure variation and the change in stroke index/cardiac index after a fluid challenge. When reported, the receiver operating characteristic of the central venous pressure, global end-diastolic volume index, and left ventricular end-diastolic area index were also recorded. Meta-analytic techniques were used to summarize the data. Twenty-nine studies (which enrolled 685 patients) met our inclusion criteria. Overall, 56% of patients responded to a fluid challenge. The pooled correlation coefficients between the baseline pulse pressure variation, stroke volume variation, systolic pressure variation, and the change in stroke/cardiac index were 0.78, 0.72, and 0.72, respectively. The area under the receiver operating characteristic curves were 0.94, 0.84, and 0.86, respectively, compared with 0.55 for the central venous pressure, 0.56 for the global end-diastolic volume index, and 0.64 for the left ventricular end-diastolic area index. The mean threshold values were 12.5 ± 1.6% for the pulse pressure variation and 11.6 ± 1.9% for the stroke volume variation. The sensitivity, specificity, and diagnostic odds ratio were 0.89, 0.88, and 59.86 for the pulse pressure variation and 0.82, 0.86, and 27.34 for the stroke volume variation, respectively. Conclusions:Dynamic changes of arterial waveform-derived variables during mechanical ventilation are highly accurate in predicting volume responsiveness in critically ill patients with an accuracy greater than that of traditional static indices of volume responsiveness. This technique, however, is limited to patients who receive controlled ventilation and who are not breathing spontaneously.

Does the Central Venous Pressure Predict Fluid Responsiveness? An Updated Meta-Analysis and a Plea for Some Common Sense*

Background:Despite a previous meta-analysis that concluded that central venous pressure should not be used to make clinical decisions regarding fluid management, central venous pressure continues to be recommended for this purpose. Aim:To perform an updated meta-analysis incorporating recent studies that investigated indices predictive of fluid responsiveness. A priori subgroup analysis was planned according to the location where the study was performed (ICU or operating room). Data Sources:MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. Study Selection:Clinical trials that reported the correlation coefficient or area under the receiver operating characteristic curve (AUC) between the central venous pressure and change in cardiac performance following an intervention that altered cardiac preload. From 191 articles screened, 43 studies met our inclusion criteria and were included for data extraction. The studies included human adult subjects, and included healthy controls (n = 1) and ICU (n = 22) and operating room (n = 20) patients. Data Extraction:Data were abstracted on study characteristics, patient population, baseline central venous pressure, the correlation coefficient, and/or the AUC between central venous pressure and change in stroke volume index/cardiac index and the percentage of fluid responders. Meta-analytic techniques were used to summarize the data. Data Synthesis:Overall 57% ± 13% of patients were fluid responders. The summary AUC was 0.56 (95% CI, 0.54–0.58) with no heterogenicity between studies. The summary AUC was 0.56 (95% CI, 0.52–0.60) for those studies done in the ICU and 0.56 (95% CI, 0.54–0.58) for those done in the operating room. The summary correlation coefficient between the baseline central venous pressure and change in stroke volume index/cardiac index was 0.18 (95% CI, 0.1–0.25), being 0.28 (95% CI, 0.16–0.40) in the ICU patients, and 0.11 (95% CI, 0.02–0.21) in the operating room patients. Conclusions:There are no data to support the widespread practice of using central venous pressure to guide fluid therapy. This approach to fluid resuscitation should be abandoned.

Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis.

OBJECTIVES:Several studies have raised concern regarding the possible association between proton-pump inhibitors (PPIs) and Clostridium difficile infection (CDI). We aimed to perform a systematic review of incident and recurrent CDI in PPI users, and to evaluate the relative impact of concurrent antibiotic use, or switching acid suppression to histamine-2-receptor antagonists (H2RAs).METHODS:We searched MEDLINE and EMBASE from inception to December 2011 for controlled observational studies that reported on the risk of CDI with and without PPI use. We performed random effects meta-analysis and assessed statistical heterogeneity using the I2 statistic.RESULTS:We included 42 observational studies (30 case-control, 12 cohort) totalling 313,000 participants overall. Pooled analysis of 39 studies showed a statistically significant association between PPI use and risk of developing CDI, odds ratio (OR) 1.74 (95% confidence interval (CI) 1.47–2.85, P<0.001, I2=85%) compared with non-users. A pooled analysis of three studies showed a significant associated risk of recurrent CDI associated with PPIs, OR 2.51 (95% CI 1.16–5.44, P=0.005, I2=78%). Subgroup analysis failed to fully clarify the source of the substantial statistical heterogeneity. Adjusted indirect comparison demonstrated that use of H2RAs as an alternative carried a lower-risk OR 0.71 (95% CI 0.53–0.97) compared with PPIs. Conversely, concomitant use of PPI and antibiotics conferred a greater-risk OR 1.96 (95% CI 1.03–3.70) above that of PPIs alone. For PPI and antibiotics, the Rothmans synergy index was 1.36 and attributable proportion of risk from interaction 0.19, indicating an increased risk from interaction beyond the effects of each drug alone.CONCLUSIONS:Despite the substantial statistical and clinical heterogeneity, our findings indicate a probable association between PPI use and incident and recurrent CDI. This risk is further increased by concomitant use of antibiotics and PPI, whereas H2RAs may be less harmful.

Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies

Background The effect of inhaled corticosteroids (ICS) on fracture risk in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to evaluate the association between ICS and fractures in COPD. Methods MEDLINE, EMBASE, regulatory documents and company registries were searched up to August 2010. Randomised controlled trials (RCTs) of budesonide or fluticasone versus control treatment for COPD (≥24 weeks duration) and controlled observational studies reporting on fracture risk with ICS exposure vs no exposure in COPD were included. Peto OR meta-analysis was used for fracture risk from RCTs while ORs from observational studies were pooled using the fixed effect inverse variance method. Dose–response analysis was conducted using variance-weighted least squares regression in the observational studies. Heterogeneity was assessed using the I2 statistic. Results Sixteen RCTs (14 fluticasone, 2 budesonide) with 17 513 participants, and seven observational studies (n=69 000 participants) were included in the meta-analysis. ICSs were associated with a significantly increased risk of fractures (Peto OR 1.27; 95% CI 1.01 to 1.58; p=0.04; I2=0%) in the RCTs. In the observational studies, ICS exposure was associated with a significantly increased risk of fractures (OR 1.21; 95% CI 1.12 to 1.32; p<0.001; I2=37%), with each 500 μg increase in beclomethasone dose equivalents associated with a 9% increased risk of fractures, OR 1.09 (95% CI 1.06 to 1.12; p<0.001). Conclusion Among patients with COPD, long-term exposure to fluticasone and budesonide is consistently associated with a modest but statistically significant increased likelihood of fractures.

Association between time of admission to the ICU and mortality: a systematic review and metaanalysis.

BACKGROUND The organizational and staffing structure of an ICU influences the outcome of critically ill and injured patients. A change in the ICU staffing structure frequently occurs at nighttime and on weekends (off-hours). We postulated that patients who are admitted to an ICU during off hours may be at an increased risk of death. METHODS We performed a systematic review of the literature to assess whether admission to an ICU during off-hours is associated with an increased mortality. We selected studies that evaluated the association between time of admission to the ICU and mortality, with adjustment for severity of disease. We excluded studies that included pediatric and non-ICU patients. Study characteristics extracted included date of publication, study design, country where study was done, study population, time factor (weekend or night shift), severity adjustment tool, and outcome. RESULTS Ten cohort studies met our inclusion criteria; eight of these studies evaluated nighttime admissions, whereas six studies evaluated weekend admissions. The pooled analysis demonstrated that nighttime admission was not associated with an increased mortality (odds ratio [OR], 1.0 [95% CI, 0.87-1.17]; P = .956); however, patients admitted over the weekend had a significant increase in the adjusted risk of death (OR, 1.08 [95% CI, 1.04-1.13]; P < .001). Significant heterogeneity was found in the studies that evaluated nighttime admissions. CONCLUSIONS Whereas patients admitted to an ICU over the weekend appear to be at an increased risk of death, nighttime admissions were not associated with an increased mortality. The lower level of staffing and intensity of care provided by many hospitals over the weekend may account for this finding. The heterogeneity noted between studies evaluating nighttime admissions likely reflects the diverse organizational structure of the hospitals and ICUs where these studies were carried out.

Obstructive Sleep Apnea Syndrome and Postoperative Complications: Clinical Use of the STOP-BANG Questionnaire

OBJECTIVE To determine whether high risk scores on preoperative STOP-BANG (Snoring, Tiredness during daytime, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, Gender) questionnaires during preoperative evaluation correlated with a higher rate of complications of obstructive sleep apnea syndrome (OSAS). DESIGN Historical cohort study. SETTING Thomas Jefferson University Hospital, Philadelphia, Pennsylvania. PATIENTS Adult patients undergoing elective surgery at a tertiary care center who were administered the STOP-BANG questionnaire for 3 consecutive days in May 2008. MAIN OUTCOME MEASURES Number and types of complications. RESULTS A total of 135 patients were included in the study, of whom 56 (41.5%) had high risk scores for OSAS. The mean (SD) age of patients was 57.9 (14.4) years; 60 (44.4%) were men. Patients at high risk of OSAS had a higher rate of postoperative complications compared with patients at low risk (19.6% vs 1.3%; P < .001). Age, American Society of Anesthesiologists class of 3 or higher, and obesity were associated with an increased risk of postoperative complications. On multivariate analysis, high risk of OSAS and American Society of Anesthesiologists class 3 or higher were associated with higher odds of complications. CONCLUSION The STOP-BANG questionnaire is useful for preoperative identification of patients at higher than normal risk for surgical complications, probably because it identifies patients with occult OSAS.

Delirium in the ICU: an overview

Delirium is characterized by a disturbance of consciousness with accompanying change in cognition. Delirium typically manifests as a constellation of symptoms with an acute onset and a fluctuating course. Delirium is extremely common in the intensive care unit (ICU) especially amongst mechanically ventilated patients. Three subtypes have been recognized: hyperactive, hypoactive, and mixed. Delirium is frequently undiagnosed unless specific diagnostic instruments are used. The CAM-ICU is the most widely studied and validated diagnostic instrument. However, the accuracy of this tool may be less than ideal without adequate training of the providers applying it. The presence of delirium has important prognostic implications; in mechanically ventilated patients it is associated with a 2.5-fold increase in short-term mortality and a 3.2-fold increase in 6-month mortality. Nonpharmacological approaches, such as physical and occupational therapy, decrease the duration of delirium and should be encouraged. Pharmacological treatment for delirium traditionally includes haloperidol; however, more data for haloperidol are needed given the paucity of placebo-controlled trials testing its efficacy to treat delirium in the ICU. Second-generation antipsychotics have emerged as an alternative for the treatment of delirium, and they may have a better safety profile. Dexmedetomidine may prove to be a valuable adjunctive agent for patients with delirium in the ICU.

Viral infection in community-acquired pneumonia: a systematic review and meta-analysis

The advent of PCR has improved the identification of viruses in patients with community-acquired pneumonia (CAP). Several studies have used PCR to establish the importance of viruses in the aetiology of CAP. We performed a systematic review and meta-analysis of the studies that reported the proportion of viral infection detected via PCR in patients with CAP. We excluded studies with paediatric populations. The primary outcome was the proportion of patients with viral infection. The secondary outcome was short-term mortality. Our review included 31 studies. Most obtained PCR via nasopharyngeal or oropharyngeal swab. The pooled proportion of patients with viral infection was 24.5% (95% CI 21.5–27.5%). In studies that obtained lower respiratory samples in >50% of patients, the proportion was 44.2% (95% CI 35.1–53.3%). The odds of death were higher in patients with dual bacterial and viral infection (OR 2.1, 95% CI 1.32–3.31). Viral infection is present in a high proportion of patients with CAP. The true proportion of viral infection is probably underestimated because of negative test results from nasopharyngeal or oropharyngeal swab PCR. There is increased mortality in patients with dual bacterial and viral infection. Viral infection is present in a high proportion of patients with community-acquired pneumonia http://ow.ly/X03pK

Contrasting Inflammatory Responses in Severe and Non-severe Community-acquired Pneumonia

The objective of this study was to compare systemic and local cytokine profiles and neutrophil responses in patients with severe versus non-severe community-acquired pneumonia (CAP). Hospitalized patients with CAP were grouped according to the pneumonia severity index (PSI), as non-severe (PSI < 91 points) or severe (PSI ≥ 91 points). Blood and sputum samples were collected upon admission. Compared to non-severe CAP patients, the severe CAP group showed higher plasma levels of pro- and anti-inflammatory cytokines but in contrast, lower sputum concentrations of pro-inflammatory cytokines. Blood neutrophil functional responses were elevated in CAP patients compared to healthy controls. However, neutrophils from severe CAP patients showed reduced respiratory burst activity compared to the non-severe group. Results indicate that patients with severe CAP fail to mount a robust local pro-inflammatory response but exhibit instead a more substantial systemic inflammatory response, suggesting that a key driver of CAP severity may be the ability of the patient to generate an optimal local inflammatory response.

Bugs or Drugs: Are Probiotics Safe for Use in the Critically Ill?

Probiotics are living microorganisms which have demonstrated many benefits in prevention, mitigation, and treatment of various disease states in critically ill populations. These diseases include antibiotic-associated diarrhea, Clostridium difficile diarrhea, ventilator-associated pneumonia, clearance of vancomycin-resistant enterococci from the GI tract, pancreatitis, liver transplant, major abdominal surgery, and trauma. However, their use has been severely limited due to a variety of factors including a general naïveté within the physician community, lack of regulation, and safety concerns. This article focuses on uses for probiotics in prevention and treatment, addresses current concerns regarding their use as well as proposing a protocol for safe use of probiotics in the critically ill patient.