Miguel A. de la Cal

Survival Benefit in Critically Ill Burned Patients Receiving Selective Decontamination of the Digestive Tract: A Randomized, Placebo-Controlled, Double-Blind Trial

Objective:To evaluate whether selective digestive decontamination (SDD) reduces mortality from any cause, and the incidence of pneumonia among patients with severe burns. Summary Background Data:SDD is a prophylactic strategy to reduce infectious morbidity and mortality in critically ill patients. Two meta-analyses and a recent randomized controlled trial demonstrated a mortality reduction varying between 20% and 40%. But this technique has never been properly evaluated in severely burned patients. Methods:The design of this single-center trial was randomized, double blind, placebo controlled. Patients with burns ≥20% of total body surface and/or suspected inhalation injury were enrolled and assigned to receive SDD or placebo for the total duration of treatment in the burn intensive care unit (ICU). Results:One hundred seventeen patients were randomized and 107 were analyzed (53 in the SDD group and 54 in the placebo group). The ICU mortality was 27.8% in the placebo group and 9.4% in the SDD group in the burn ICU. Treatment with SDD was associated with a significant reduction in mortality both in the burn ICU (risk ratio 0.25; 95% CI 0.08 to 0.76) and in the hospital (risk ratio 0.28; 95% CI 0.10 to 0.80), following adjustment for predicted mortality. The incidence of pneumonia was significantly higher in the placebo group: 30.8 and 17.0 pneumonias per 1000 ventilation days (P = 0.03) in placebo and SDD group, respectively. Conclusions:Treatment with SDD reduces mortality and pneumonia incidence in patients with severe burns.

Efficacy of Corticosteroid Therapy in Patients With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease Receiving Ventilatory Support

BACKGROUND Randomized trials assessing the effect of systemic corticosteroids on chronic obstructive pulmonary disease (COPD) exacerbations excluded patients who were mechanically ventilated or admitted to the intensive care unit (ICU). Critically ill patients constitute a population of persons who are prone to develop complications that are potentially associated with the use of corticosteroids (eg, infections, hyperglycemia, ICU-acquired paresis) that could prolong the duration of mechanical ventilation and even increase mortality. METHODS A double-blind placebo-controlled trial was conducted to evaluate the efficacy and safety of systemic corticosteroid treatment in patients with an exacerbation of COPD who were receiving ventilatory support (invasive or noninvasive mechanical ventilation). A total of 354 adult patients who were admitted to the ICUs of 8 hospitals in 4 countries from July 2005 through July 2009 were screened, and 83 were randomized to receive intravenous methylprednisolone (0.5 mg/kg every 6 hours for 72 hours, 0.5 mg/kg every 12 hours on days 4 through 6, and 0.5 mg/kg/d on days 7 through 10) or placebo. The main outcome measures were duration of mechanical ventilation, length of ICU stay, and need for intubation in patients treated with noninvasive mechanical ventilation. RESULTS There were no significant differences between the groups in demographics, severity of illness, reasons for COPD exacerbation, gas exchange variables, and corticosteroid rescue treatment. Corticosteroid treatment was associated with a significant reduction in the median duration of mechanical ventilation (3 days vs 4 days; P = .04), a trend toward a shorter median length of ICU stay (6 days vs 7 days; P = .09), and significant reduction in the rate of NIV failure (0% vs 37%; P = .04). CONCLUSION Systemic corticosteroid therapy in patients with COPD exacerbations requiring mechanical ventilation is associated with a significant increase in the success of noninvasive mechanical ventilation and a reduction in the duration of mechanical ventilation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01281748.

Enteral Vancomycin Controls Methicillin-resistant Staphylococcus Aureus Endemicity in an Intensive Care Burn Unit: A 9-Year Prospective Study

Objective:The aim of this study was to assess the efficacy and safety of enteral vancomycin in controlling MRSA endemicity in an intensive care burn unit. Summary Background Data:MRSA is a serious clinical and epidemiologic problem. It is not uncommon that the traditional maneuvers, detection and isolation of carriers, fail to control endemicity due to MRSA. Methods:All patients admitted to an Intensive Care Burn unit from January 1995 to February 2004 have been included in this prospective cohort study comprised 2 different periods. During period 1 (January 1995 to January 2000), barrier and isolation measures were enforced. During period 2 (February 2000 to February 2004), patients received enteral vancomycin 4 times daily in addition to selective digestive decontamination. Results:A total of 777 patients were enrolled into the study: 402 in period 1, and 375 in period 2. There were no significant differences in the characteristics of patients between the 2 periods, except for the total body surface burned area, 30.3% in period 1 and 25.61% in period 2 (P = 0.009). There was a significant reduction in the incidence of patients who acquired MRSA from 115 in period 1 to 25 in period 2 (RR, 0.22; 95% confidence interval [CI], 0.15–0.34). Similar reductions were observed in the number of patients with wound (RR, 0.20; 95% CI, 0.12–0.32), blood (RR, 0.13; 95% CI, 0.04–0.35), and tracheal aspirate (RR, 0.07; 95% CI, 0.03–0.19), samples positive for MRSA. There was no emergence of either vancomycin-resistant enterococci or Staphylococcus aureus with intermediate sensitivity to glycopeptides in period 2. Conclusions:Enteral vancomycin is an effective and safe method to control MRSA in intensive care burn units without VRE.

Organ dysfunction as estimated by the sequential organ failure assessment score is related to outcome in critically ill burn patients.

The objectives of the study were to assess organ dysfunction in burn patients by using the Sequential Organ Failure Assessment (SOFA) score, to determine the relationship between early (day 1) and late (day 4) organ dysfunction, as well as the change in organ dysfunction from admission to day 4, and mortality. The design was a prospective observational cohort study. Patients were admitted to our intensive care burn unit with severe thermal burns (≥20% total body surface area [BSA] burned) or inhalation injury with a delay from injury to admission less than 12 h and a length of stay less than 3 days (n = 439; age, 46.0 ± 20.3 yrs; total BSA burned, 31.6% ± 20.2% [mean ± SD]; inhalation injury, 44.4%; crude mortality, 18.5%). Sequential Organ Failure Assessment scores were measured on admission (SOFA 0) and on subsequent days (SOFA 1, SOFA 2, SOFA 3, and SOFA 4). The difference between SOFA 0 and SOFA 4 (&Dgr;SOFA 0−4) was calculated. Multivariate logistic regression analyses, including other variables associated with mortality in the models, were performed to calculate adjusted odds ratios (ORs) of organ dysfunction measurements for mortality. After adjusting for age, BSA burned, diagnosis of inhalation injury, and sex, SOFA 1 (OR, 1.89; 95% confidence interval [CI], 1.55-2.32), SOFA 4 (OR, 1.33; 95% CI, 1.19-1.47), and &Dgr;SOFA 0−4 (OR, 1.40; 95% CI, 1.28-1.55) were independently associated with mortality. The SOFA score is useful to assess organ dysfunction in burn patients. Burn-induced organ dysfunction (early and late), as well as the change in organ dysfunction, is independently associated with mortality.

The emperor's new clothes: the fairy tale continues

Semirecumbency Drakulovic [5] Mixed 2/43 11/47 van Nieuwenhoven [6] Mixed 13/112 8/109 All studies 15/155 19/156 Subglottic drainage Mahul [7] Mixed 9/70 21/75 Valles [8] Mixed 14/76 25/77 Metz [9] Trauma/surgery 15/25 10/14 Kollef [10] Cardiac 8/160 15/183 Bo [11] Surgery 8/35 15/33 Smulders [12] Mixed 3/75 12/75 Lorente [13] a Mixed 11/140 31/140 All studies 68/581 129/597 Oral antiseptics DeRiso [14] Cardiac 3/173 9/180 Fourrier [15] Medical 5/30 15/30 Houston [16] Cardiac 4/270 9/291 MacNaughton [17] Mixed NR/91 NR/88 Grap [18] Mixed NR/23 NR/11 Fourrier [19] b Mixed 13/114 12/114 Segers [21] Cardiac 45/485 74/469 Seguin [22] Trauma 3/36 12/31 Koeman [20] Mixed 13/127 23/130 Bopp [23] Mixed 0/2 1/3 Tantipong [24] Mixed 5/102 12/105 All studies c 91/1399 167/1353

Un nuevo ensayo clínico con descontaminación digestiva selectiva

De Smet et al han publicado un nuevo ensayo clinico sobre descontaminacion digestiva selectiva (DDS). La DDS fue descrita en los anos ochenta como una tecnica para prevenir la infeccion respiratoria en los enfermos criticos y desde entonces se han realizado 57 ensayos clinicos con asignacion aleatoria. Por lo tanto, es la tecnica mas extensamente evaluada en las unidades de cuidados intensivos (UCI). La mejor estimacion de su efecto en la poblacion general de enfermos criticos es que la administracion del protocolo completo previene una neumonia por cada 5 enfermos tratados y una muerte por cada 21 enfermos tratados. A pesar de estos efectos beneficiosos, no se ha generalizado el uso de DDS porque los expertos aducen, en contra de la evidencia existente, que: a) la reduccion de la mortalidad es heterogenea en los diferentes ensayos clinicos, y b) puede conllevar un aumento de la resistencia antibiotica. De Smet et al presentan los resultados de un ensayo clinico, realizado en 13 centros de los Paises Bajos, que incluye a 6.000 pacientes. Sus objetivos fueron comparar el impacto en la mortalidad y la resistencia antibiotica de la aplicacion del protocolo completo de DDS contra la descontaminacion solo orofaringea —polimixina, tobramicina, anfotericina— y contra placebo.De Smet et al han publicado un nuevo ensayo clínico sobre descontaminación digestiva selectiva (DDS). La DDS fue descrita en los años ochenta como una técnica para prevenir la infección respiratoria en los enfermos críticos y desde entonces se han realizado 57 ensayos clínicos con asignación aleatoria. Por lo tanto, es la técnica más extensamente evaluada en las unidades de cuidados intensivos (UCI). La mejor estimación de su efecto en la población general de enfermos críticos es que la administración del protocolo completo previene una neumonía por cada 5 enfermos tratados y una muerte por cada 21 enfermos tratados. A pesar de estos efectos beneficiosos, no se ha generalizado el uso de DDS porque los expertos aducen, en contra de la evidencia existente, que: a) la reducción de la mortalidad es heterogénea en los diferentes ensayos clínicos, y b) puede conllevar un aumento de la resistencia antibiótica. De Smet et al presentan los resultados de un ensayo clínico, realizado en 13 centros de los Países Bajos, que incluye a 6.000 pacientes. Sus objetivos fueron comparar el impacto en la mortalidad y la resistencia antibiótica de la aplicación del protocolo completo de DDS contra la descontaminación sólo orofaríngea —polimixina, tobramicina, anfotericina— y contra placebo.

Surviving Sepsis Campaign needed consensus to exclude selective decontamination of the digestive tract.

To the Editor: We thank Dr. MacIntyre for his editorial (1) on our article (2). We have four questions for him. One, we identified more than 15 methodologic errors in the metaanalysis performed by the EvidenceBased-Medicine Task Force on weaning (3). Our article holds no importance if we are wrong about the methodologic errors we identified (2). Dr. MacIntyre does not contend a single one of these errors. He writes “I’m not going to address the methodologic criticisms” (1). Yet, this is the very core of our article. The primary means for correcting scientific error is the dialectic process (4). Avoiding engagement in argument and counter-argument is the antithesis of science (4). We ask Dr. MacIntyre: “If we mistakenly identified some methodologic errors, which ones are they?” (Dr. MacIntyre writes “the methodologic criticisms [are] addressed in accompanying editorial”. But Dr. Marini did not write that we made methodologic errors). Two, Dr. MacIntyre continues, “Rather I will clarify how the McMaster findings were used by the task force to create operational guidelines for clinicians at the bedside.” (1) In this sentence, Dr. MacIntyre implies that the Task Force created clinical guidelines without analyzing the primary data (5). Our questions to Dr. MacIntyre: “Did Task-Force members check for errors in the analyses undertaken by the McMaster group?” (If the Task Force’s primary role was to imprint a seal-of-approval on a metaanalysis conducted by another group, readers should be so informed). Three, Dr. MacIntyre notes their meta-analysis revealed “consistently significant likelihood ratios” (1). But consistency is no guard against systematic error. If a spirometer contains a positive bias, the recorded volumes will overestimate true volume in a “consistent” manner (2). Dr. MacIntyre writes “the task force concluded that the individual likelihood ratios were not sufficiently high enough to drive clinical decision making at the bedside.” (1) We ask Dr. MacIntyre: “Is it wise to drive clinical decisions based on likelihood ratios that involve a series of compounded methodologic errors?” Four, Dr. MacIntyre writes “The guidelines seem to be standing the ‘test of time’ and are continuing to serve as an important tool to reduce iatrogenic delays in mechanical ventilation withdrawal.” (1) We ask Dr. MacIntyre: “If these are not mere assertions, please present the data that warrant your conclusion: that the guidelines are (a) standing the test of time and (b) reducing iatrogenic weaning delays?” We listed more than 15 methodologic errors in the Task Force’s meta-analysis (2). If we are wrong about these, we welcome correction from any member of the Task Force (3, 5). If the methodologic errors cannot be refuted, then what is the validity of the evidence on which the Evidence-Based-Medicine Task Force base their conclusions? The authors have not disclosed any potential conflicts of interest.

Selective decontamination of the digestive tract in burn patients: an evidence-based maneuver that reduces mortality.

We would like to thank Dr. Silvestri et al for their comments on selective decontamination of the digestive tract (SDD) in burn patients. Their detailed review of available data in burn patients will prove informative to burn practitioners throughout the world. We agree that multiple SDD trials have indicated benefit in decreasing ventilator-associated pneumonia incidence and reducing mortality in surgical patients, including burns. We have tried to make that point clear in our guidelines. Despite multiple positive SDD trials conducted in Europe and elsewhere, this practice has gained little support in intensive care units (ICUs) in the United States. We believe the deterrents to widespread acceptance of SDD in North America have been 1) heterogeneity of methods for decontamination, 2) inconsistent results in surgical patient populations, and, most importantly, 3) the fear that it will promote emergence and spread of antimicrobial resistant microorganisms. To better understand the impact of systematic antibiotic administration to large patient cohorts, longitudinal ecological ICU studies are also needed to substantiate the efficacy observed in the reported clinical trials. Interestingly, although the recent Dutch multicenter trial demonstrated a decreased incidence of multiresistant organisms on rectal cultures with SDD, its follow-up ecological study in the 13 participating ICUs now reports a twofold increase in the incidence of antibiotic resistance in the intestinal and the respiratory tracts. These findings are consistent with prior studies, indicating major shifts in the microbial ecology of the ICU with SDD. We, thus, believe that our caution against “the prophylactic use of antibiotics in units with high levels of antibiotic resistance” remains justified in light of the aggregate data. We believe the best way to resolve this controversy and impact practice patterns would be a prospective, randomized trial of SDD in burn ICUs recruited from multiple countries.

Prevention of nosocomial infection in the intensive care unit

Traditional approaches to definitions of nosocomial infections and their prophylaxis focus on time cut-offs and nonantibiotic maneuvers. In general, the time cut-off of 48 hours has been applied to distinguish community and hospital infection from intensive care unit (ICU) infection, and hand washing has been the cornerstone of conventional policies for the prevention of ICU infections occurring after 48 hours. In contrast, the philosophy of antibiotic prophylaxis using selective decontamination of the digestive tract is based on the criterion of the carrier state of a limited range of potential pathogens that are involved in three different types of infection: endogenous infections, both primary and secondary, and exogenous infections. Most infections are of primary endogenous development due to microorganisms carried in the admission flora and are controlled by the parenteral cefotaxime administered immediately on admission. The aim of polymyxin E/tobramycin/amphotericin B applied topically in the throat and gut is to prevent secondary endogenous infections due to microorganisms acquired on the unit, and generally occurring after 7 days. Exogenous infections caused by microorganisms not previously carried can occur at any time during the stay on the unit and only high standards of hygiene are able to prevent them. The most extensive meta-analysis reports data on 5,727 patients enrolled in 33 randomized trials and indicates a significant reduction of both infections (OR = 0.35; 95% CI = 0.29–0.41) and total mortality (OR = 0.80; 95% CI = 0.69–0.93). No randomized trials showing that rigid implementation of hand washing reduces morbidity or mortality are available. The aim of this review is to help readers distinguish between what is evidence-based and what is still largely opinion-based.

Selective Digestive Decontamination Attenuates Organ Dysfunction in Critically Ill Burn Patients

Objective: To evaluate whether selective decontamination of the digestive tract (SDD) attenuates organ dysfunction in critically ill burn patients. Background: The effect of SDD on the development and progression of organ dysfunction, as an important determinant of mortality in burned patients, is still unknown. We asked whether organ dysfunction is mitigated by treatment with SDD. Methods: Patients with burns >20% of total body surface or suspected inhalation injury from a randomized placebo-controlled trial were analyzed to determine the relationship between treatment received (placebo or SDD) and the severity of organ dysfunction as measured by the area under the curve of the Sequential Organ Failure Assessment (SOFA) score (and its individual components) from day 1 to day 7 of admission. Results: One hundred seven patients (53 in the SDD group and 54 in the placebo group) were included. Survival was significantly higher in SDD-treated patients (48 of 53, 90.6%) than in placebo-treated patients (39 of 54, 72.2%, P = 0.013). Total (P < 0.01) and respiratory (P < 0.01), cardiovascular (P = 0.04) and hematological (not reaching statistical significance, P = 0.07) organ dysfunction was associated with mortality after adjusting for predicted mortality. In multivariate logistic regression, SDD treatment was independently associated with total (P < 0.01), respiratory (P = 0.02), and hematological (P < 0.01) dysfunction over the first week postinjury. Conclusions: The beneficial effect of SDD on mortality in critically ill burned patients is accompanied by a reduction in the degree of organ dysfunction. SDD seems to be a valuable therapeutic strategy to prevent organ dysfunction and, more specifically, respiratory and hematological dysfunction in severely ill burn patients.