Hendrick K. F. van Saene

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.

Selective decontamination of the digestive tract in cardiac surgical patients.

ObjectiveTo test the hypothesis that selective decontamination of the digestive tract improves outcome in cardiac surgical patients. DesignProspective, consecutive, controlled trial over two 4-month periods. SettingEight-bed, open-plan postcardiac surgery ICU. PatientsAll patients undergoing cardiac bypass surgery were eligible. Patients requiring endotracheal intubation for >4 days were included in the analysis. In the initial 4 months, 12 (8.5%) of 141 patients required >4 days of intubation. These 12 patients were not treated with selective decontamination of the digestive tract. We therefore used these patients as the control group. In the second 4-month period, 12 (6.6%) of 180 patients were treated with selective decontamination of the digestive tract and formed the study group. Main Outcome MeasuresThe primary measure was mortality. Secondary measures included oropharyngeal decontamination and the presence of lower airway infection. InterventionsCephradine prophylaxis. The study group received every 6 hrs 4 mL orally and 20 mL intragastrically a suspension of antimicrobial agents (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg), starting on postoperative day 1. The control group did not receive any oral antimicrobial agents. ResultsMortality rate was significantly (p < .05) reduced from eight (66%) of 12 patients in the control group to two (16.7%) of 12 patients in the selective decontamination of the digestive tract group. No differences in oropharyngeal decontamination or lower airway infection rates between the two groups were found. ConclusionsThere is a reduced mortality rate in patients receiving selective decontamination of the digestive tract. However, the reader should recognize the small sample size studied. A simple suspension of the antimicrobial agents failed to rid the oropharynx of bacteria.

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.

Survival benefit of the full selective digestive decontamination regimen

PURPOSE We assessed the impact of the full protocol of selective decontamination of the digestive tract (SDD) using parenteral and enteral antimicrobials on mortality. MATERIALS AND METHODS A systematic review was performed searching MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, previous meta-analyses, and conferences proceedings. We included all randomized controlled trials (RCTs) comparing the full protocol of SDD, including oropharyngeal and intestinal administration of antibiotics combined with the parenteral component, with no treatment or placebo. The primary end points were overall mortality, mortality attributable to infection, early, and late mortality. RESULTS Twenty-one RCTs on 4902 patients were included. Overall mortality was significantly reduced (odds ratio [OR], 0.71; 95% confidence interval [CI]; 0.61-0.82; P < .001). There was a nonsignificant reduction in infection-related mortality (6 RCTs; OR, 0.40; 95% CI, 0.10-1.59; P = .19) and early mortality (4 RCTs; OR, 0.64; 95% CI, 0.34-1.19; P = 0.16), and a significant reduction in late mortality (5 RCTs; OR, 0.56; 95% CI, 0.40-0.77; P < .001). The subgroup analysis showed a significant mortality reduction in successfully decontaminated patients (OR, 0.58; 95% CI, 0.45-0.77; P < .001), and when parenteral and enteral antimicrobials were administered to every patient receiving treatment in the intensive care unit (OR, 0.59; 95% CI, 0.42-0.82; P < .001). CONCLUSIONS The findings strongly indicated that the full protocol of SDD reduces mortality in critically ill patients, in particular when successful decontamination is obtained. Eighteen patients should be treated with SDD to prevent one death.

Impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome: Systematic review of randomized controlled trials

Objective:We examined the impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome. Data Sources:We searched MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, previous meta-analyses, and meetings proceedings. Study Selection:We included all randomized trials comparing both oropharyngeal and intestinal administration of antibiotics in selective decontamination of the digestive tract with or without a parenteral component, with placebo or standard therapy used in the controls. Data Extraction:Two reviewers independently applied selection criteria, performed quality assessment, and extracted the data. The primary end point was the number of patients with multiple organ dysfunction syndrome developing during intensive care unit stay. Secondary end points were overall mortality and multiple organ dysfunction syndrome-related mortality. Odds ratios were pooled with the random effect model. Data Synthesis:We identified seven randomized trials including 1270 patients. Multiple organ dysfunction syndrome was found in 132 of 637 patients (20.7%) in the selective decontamination of the digestive tract group and in 219 of 633 patients (34.6%) in the control group (odds ratio, 0.50; 95% confidence interval, 0.34–0.74; p < .001). Overall mortality for selective decontamination of the digestive tract vs. control patients was 119 of 637 (18.7%) and 145 of 633 (22.9%), respectively, demonstrating a nonsignificant reduction in the odds of death (odds ratio, 0.82; 95% confidence interval, 0.51–1.32; p = .41). In five studies including 472 patients, multiple organ dysfunction syndrome-related mortality was demonstrated in 31 of 239 (13%) patients in selective decontamination of the digestive tract group and 37 of 233 (15.9%) in the controls (odds ratio, 0.84; 95% confidence interval, 0.48–1.41; p = .54). Conclusions:Selective decontamination of the digestive tract reduces the number of patients with multiple organ dysfunction syndrome. Mortality was not significantly reduced, probably because of the small sample size.

SDD, SOD, or oropharyngeal chlorhexidine to prevent pneumonia and to reduce mortality in ventilated patients: which manoeuvre is evidence-based?

Dear editor: We read with interest the editorial by Segers and de Mol on the prevention of ventilator-associated pneumonia (VAP) after cardiac surgery [1]. We would like to comment on the authors’ statements on the use of selective digestive decontamination (SDD), selective oropharyngeal decontamination (SOD), and oropharyngeal chlorhexidine, as they are based on inaccurate interpretation of the evidence. The authors refer to a large SDD/ SOD study [2] which showed a significant reduction in the odds for mortality of SDD and SOD compared to standard care of 16% (odds ratio [OR] 0.835, 95% confidence interval [CI] 0.72–0.968, P = 0.016) and 14% (OR 0.858, 95% CI 0.739–0.996, P = 0.045), respectively. The reduction in mortality was higher in the SDD group than in the SOD group, albeit not significantly. There are nine randomized controlled trials (RCTs) evaluating the impact of SOD on lower respiratory tract infection and mortality. We performed a metaanalysis of those RCTs showing that SOD significantly reduces lower respiratory tract infections, but not mortality (Table 1). Contrastingly, there is robust evidence from the literature which indicates that the full SDD regimen of parenteral and enteral antimicrobials significantly reduces morbidity, i.e. pneumonia [3] and bloodstream infection [4], and mortality [3, 5]. The authors advocate the use of SOD instead of SDD ‘‘because it does not include widespread systemic prophylaxis with cephalosporins and involves a lower volume of topical antibiotics, thus minimizing the risk of development of antibiotic resistance’’. However, the Dutch study [2] clearly shows that patients with Gram-negative bacteria in rectal swabs resistant to the marker antibiotics are lower with SDD than with SOD. These results confirm that the resistance problem is not a function of intestinally applied volume of antimicrobials, but of systemically administered antibiotics. Remarkably, the use of all systemic antibiotics was higher in the SOD group than in the SDD group. Finally, the Dutch study confirms the findings that SDD does not increase the resistance problem, but actually reduces it [3]. The authors recommend the use of oropharyngeal chlorhexidine in cardiac surgery. Of the five metaanalyses of oropharyngeal chlorhexidine, three demonstrated a significant reduction in pneumonia, but none showed a significant reduction in mortality (see S1 in the Electronic Supplementary Material). The metaanalysis of the only three RCTs of chlorhexidine in cardiac surgery shows that chlorhexidine significantly reduces lower respiratory tract infections (Table 1). However, this result should be cautiously interpreted, as the duration of mechanical ventilation was short, and those studies reported the incidence of nosocomial pneumonia, not that of VAP, e.g. most patients received only few doses of the oral rinsing agent because extubation occurred within 4–12 h after surgery. Again, mortality is not significantly reduced by chlorhexidine. Therefore, although we welcome the authors’ claim of ‘‘prepare and defend’’, we advocate prevention of pneumonia using evidence based medicine (EBM) manoeuvres. SDD is the only EBM manoeuvre which has been shown to significantly reduce severe infections, i.e. pneumonia and bloodstream infection, and mortality, whilst SOD and oropharyngeal chlorhexidine still require further investigation.

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.

Selective decontamination of the digestive tract in critically ill children: systematic review and meta-analysis.

Objective: We examined the impact of selective decontamination of the digestive tract on morbidity and mortality in critically ill children. Data Sources: We searched MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, and previous meta-analyses. Study Selection: We included all randomized controlled trials comparing administration of enteral antimicrobials in selective decontamination of the digestive tract with or without a parenteral component with placebo or standard therapy used in the controls. Data Extraction: The primary end point was the number of acquired pneumonias. Secondary end points were number of infections and overall mortality. Odds ratios were pooled with the random effect model. Data Synthesis: Four randomized controlled trials including 335 patients were identified. Pneumonia was diagnosed in five of 170 patients (2.9%) for selective decontamination of the digestive tract and 16 of 165 patients (9.7%) for controls (odds ratio 0.31; 95% confidence interval 0.11–0.87; p = .027). Overall mortality for selective decontamination of the digestive tract was 13 of 170 (7.6%) vs. control, 11 of 165 (6.7%) (odds ratio 1.18; 95% confidence interval 0.50–2.76; p = .70). In three studies (n = 109), infection occurred in ten of 54 (18.5%) patients on selective decontamination of the digestive tract and 24 of 55 (43.6%) in the controls (odds ratio 0.34; 95% confidence interval 0.05–2.18; p = .25). Conclusions: In the four available pediatric randomized controlled trials, selective decontamination of the digestive tract significantly reduced the number of children who developed pneumonia.

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.