D. F. Zandstra

The virtual absence of stress-ulceration related bleeding in ICU patients receiving prolonged mechanical ventilation without any prophylaxis : a prospective cohort study

ObjectiveTo study the incidence of stress-ulcer related bleeding in ICU patients receiving prolonged (>2 days) mechanical ventilation without any stress ulceration prophylaxis.DesignA prospective cohort study in 183 patients.InterventionsAll patients received clinical treatment including maintenance of adequate tissue perfusion (with low dose inotropes and vasodilators), infection prevention (by selective decontamination of the digestive tract) throughout ICU stay and suppression of generalized inflammatory reaction (by steroids).SettingMedical/surgical ICU of a major teaching hospital in Amsterdam (Onze Lieve Vrouwe Gasthuis).Measurements and results167 patients were evaluated during 2182 treatment days in the ICU and during 1753 days on mechanical ventilation without stress ulceration prophylaxis. The mean total risk score for stress ulcetation related bleeding was 38 (Tryba score). Stress ulceration realted bleeding developed in 1 patient (0.6%).ConclusionsThe incidence of SURB was less then 1% in this cohort of ICU patients receiving longterm mechanical ventilation with a high risk for SURB (mean total risk score 38). All patients received agressive shock resuscitation, infection prevention with selective decontamination of the digestive tract (SDD) and suppression of inflammatory response with steroids. Further studies are needed to evaluate the contribution of each of these elements of the integral approach.

Selective decontamination of the digestive tract: 13 years on, what it is and what it is not

Selective decontamination of the digestive tract (SDD) is a prophylactic strategy designed to prevent or minimise the impact of both endogenous and exogenous infections by potentially pathogenic micro-organisms (PPM) in patients admitted to the intensive care unit (ICU). It was introduced in 1983 and has received considerable attention, especially in Europe, some of it favourable and some critical. By mid-1996, SDD had been assessed in 46 controlled trials and evaluated by various reviews. On balance, when properly used, SDD significantly reduces infectious morbidity, in particular respiratory tract infections by 65% and mortality by 20% [1, 2]. Despite being the best ever evaluated manoeuvre in intensive care medicine and one of the few interventions subjected to scientific and statistical appraisal, SDD is still controversial due to issues including the following: (a) five negative SDD trials, which are always mentioned in discussion, (b) the moderate irapact on mortality and (c) the fear of the emergence of antimicrobial resistance, despite the lack of any evidence after one decade [3]. However, our concern here is with those who have been disappointed with or even explicitly critical of SDD while at the same time failing to recognise the full SDD protocol or realise inherent limitations. Despite the need for precise definition of the terms used in describing and analysing SDD, there is still some ambiguity, to which we have unfortunately contributed. Here, we take the opportunity, provided by the 13th anniversary of the introduction of SDD, to clarify the definition in the hope that future ambiguity and confusion may be prevented.

Nosocomial gram-negative pneumonia in critically ill patients

The efficacy of selective decontamination of the oral cavity and GI-tract in the treatment of established gram-negative pneumonia in critically ill patients was evaluated in a prospective open trial. 25 patients with pneumonia caused by Enterobacteriaceae or Pseudomonadaceae were studied. All patients were mechanically ventilated (range 2–60 days). Non-absorbable antibiotics (polymyxin E 100 mg, tobramycin 80 mg, amphotericin B 500 mg) were administered through the nasogastric tube four times a day. The oral cavity was decontaminated with an ointment containing 2% of the same antibiotics, applied to the buccal mucosa four times a day. For systemic therapy a combination of tobramycin (3–6 mg · kg-1) with either cefotaxim (50–100 mg · kg-1) or ceftazidime (100 mg · kg-1) was given both intravenously and by aerosol (50% IV dose/5 ml saline) four times a day. Eradication of pathogens from the respiratory tract was achieved in 24 patients within 9 days (median 5 days). The cure rate was 96%. Two patients had a relapse. Neither recolonization with resistant organisms nor supra-infections were found for the remaining period of mechanical ventilation (up to 60 days), also after systemic/aerosol therapy had been discontinued. Only 3 patients died (12%).

ARDS of Early or Late Onset: Does It Make a Difference?

BACKGROUNDnDifferences in outcomes have been demonstrated for critically ill patients with late-onset compared with early-onset renal failure and late-onset compared with early-onset shock, which could cause a lead-time bias in clinical trials assessing potential therapies for these conditions. We used data from a large, multicenter observational study to assess whether late-onset ARDS was similarly associated with worse outcomes compared with early-onset ARDS.nnnMETHODSnData were extracted from the Sepsis Occurrence in Acutely Ill Patients (SOAP) study, which involved 198 ICUs from 24 European countries. All adult patients admitted to a participating ICU between May 1, 2002 and May 15, 2002, were eligible, except those admitted for uncomplicated postoperative surveillance. Early/late onset acute lung injury (ALI)/ARDS was defined as ALI/ARDS occurring within/after 48 h of ICU admission.nnnRESULTSnOf the 3,147 patients included in the SOAP study, 393 (12.5%) had a diagnosis of ALI/ARDS; 254 had early-onset ALI/ARDS (64.6%), and 139 (35.5%) late-onset. Patients with early-onset ALI/ARDS had higher Simplified Acute Physiology II scores on admission and higher initial Sequential Organ Failure Assessment scores. Patients with late-onset ALI/ARDS had longer ICU and hospital lengths of stay than patients with early-onset ALI/ARDS. ICU and hospital mortality rates were, if anything, lower in late-onset ALI/ARDS than in early-onset ALI/ARDS, but these differences were not statistically significant.nnnCONCLUSIONSnThere were no significant differences in mortality rates between early- and late-onset ARDS, but patients with late-onset ALI/ARDS had longer ICU and hospital lengths of stay.

Selective decontamination of the digestive tract: rationale behind evidence-based use in liver transplantation.

Selective decontamination of the digestive tract (SDD) is a prophylactic strategy designed to prevent or minimize the impact of endogenous infections by potentially pathogenic microorganisms (PPM) in patients at high risk of infection.1 The purpose of SDD is to prevent or eradicate, if initially present, oropharyngeal and gastrointestinal carriage of PPM, especially aerobic gram-negative bacilli (AGNB), but also Staphylococcus aureus and yeasts, leaving the indigenous flora, which are thought to play a role in the resistance to colonization by PPM, predominantly undisturbed.2 The overall aim is a reduction in morbidity and mortality. The physiological phenomenon that the normal, mainly anaerobic flora is required to control the abnormal aerobic PPM was recognized early, after the introduction of antimicrobial agents.3 Antibiotics active against anaerobes and excreted in the gut may suppress the normal indigenous flora. They disregard the ecology and may cause candidiasis of mouth, vagina, and groin.4 These flora-suppressing antimicrobials promote yeast overgrowth, defined as 10 colony-forming units per milliliter of saliva and per gram of feces, following the excretion of microbiologically active antibiotic concentrations into the throat and/or gut via saliva, bile, and mucus. The need to preserve the normal indigenous flora was also acknowledged for controlling overgrowth of S. aureus5 and AGNB.6 Previous antibiotic administration lowers the infecting doses of high-level enteric pathogens Salmonella7 species and Clostridium difficile.8 More recently, overgrowth of low-level pathogens including vancomycin-resistant enterococci (VRE) is prevented by antimicrobials that respect the gut ecology.9 In 1971, van der Waaij quantified the physiological phenomenon of the normal flora controlling the abnormal flora using challenge experiments in mice.2 He defined colonization resistance as the concentration of the bacterial challenge strain expressed by the log of colony-forming units per milliliter required to result in abnormal carriage in half the animals. Generally, healthy animals possess a high colonisation resistance of 9 as they clear high doses of 10 AGNB, including Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae, contaminating their drinking water. Antimicrobials including cephradine and cefotaxime did not promote the establishment of abnormal flora and were labelled as ecology-friendly, or “green,” antibiotics.10 The abnormal carrier state was established in 50% of the animals receiving antibiotics like ampicillin and flucloxacillin after challenging them with 10 PPM. These agents decreased the resistance of mice to colonization to 5 and were considered to be “red,” as they disregard the animal gut ecology. Amoxycillin was found to be “amber,” as only high doses lowered the colonization resistance of mice. These antimicrobials were subsequently tested in healthy volunteers also in challenge studies.11–13. Vollaard demonstrated that none of the antimicrobials were found to be completely ecology friendly.13 They invariably impacted colonization resistance. He argued that the gut ecology is an extremely fragile balance and very susceptible to antimicrobial agents. However, there were still major differences among antimicrobial agents in terms of their influence on the indigenous flora. In the volunteer studies, the disregard of ampicillin and amoxycillin for the ecology was significantly worse compared with that of cephradine and cefotaxime. Abnormal carriage with ampicillin and amoxycillin was more frequent and lasted longer compared with cephraAbbreviations: SDD, selective decontamination of the digestive tract; PPM, potentially pathogenic microorganisms; AGNB, aerobic gram-negative bacilli; VRE, vancomycin-resistant enterococci; ICU, intensive care unit; RCTs, randomized controlled trials; MRSA, methicillin-resistant Staphylococcus aureus. From the Department of Medical Microbiology, University of Liverpool, UK, and Department of Intensive Care, Onze Lieve Vrouwe Gasthius Hospital, Amsterdam, The Netherlands. Address reprint requests to HKF van Saene, M.D., Department of Medical Microbiology, University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA, United Kingdom. Telephone: 44-151-2525006; FAX: 44-151-2525356; E-mail: Rick.VanSaene@ RLCH-TR.NWEST.NHS.UK Copyright

Non-invasive pulmonary blood flow measurement by means of CO2 analysis of expiratory gases

Two different methods of CO2-derived non-invasive assessment of the pulmonary blood flow were evaluated. The principle of the formula, as proposed by Gedeon et al., is based on a rapid change in arterial CO2 content and subsequent changes in endtidal PCO2 and CO2 elimination. Both methods were compared to thermodilution cardiac output in 44 postoperative patients after CABG. The first method consisted of a short period of hyperventilation followed by hypoventilation. Comparison with the thermodilution cardiac output showed a low correlation coefficient: using a measured arterial —end-tidal PCO2 difference (E)r=0.397 was found. Entering a fixed E of 0.53 kPa resulted inr=0.454. These disappointing figures may be explained by procedural mistakes. The second method, based on partial rebreathing by means of adding an additional dead space of 220 ml for 30–45 s, correlated very well with the thermodilution findings. Correlation coefficients ofr=0.925 (measured E) andr=0.925 (fixed E) were found. Considering the simplicity of the method, the additional dead space approach seems to be an easy and reliable way to determine pulmonary blood flow.

Monitoring differential CO2 excretion during differential lung ventilation in asymmetric pulmonary contusion. Clinical implications

Eighteen severely injured polytrauma patients (ISS 38±18) with severe asymmetric pulmonary contusion were ventilated with differential lung ventilation (DLV) to improve oxygenation and/or to prevent further unnecessary barotrauma to the lesser involved lung. Differential VCO2 was studied as a parameter for indirect measurement of effective individual pulmonary perfusion. One hour after starting DLV, difference in differential VCO2 (delta VCO2) was 81±57ml/min. In 16 patients this had fallen significantly (p<0.001) to 32±30ml/min, 1 h before DLV was discontinued. In 2 patients, VCO2 remained > than 200ml/min, coinciding with clinical deterioration and increasing consolidation of the pulmonary contusion. Bilobectomies were performed in both patients. The excised lobes appeared to be destroyed as the result of laceration, bleeding and subsequent haematomas. This clinical study supports laboratory studies suggesting the usefulness of monitoring differential VCO2 to assess effective differential pulmonary perfusion during DLV.

Selective decontamination of the digestive tract: selectivity is not required

Dear Editor, n nWe read Benus and colleagues’ article entitled ‘Impact of digestive and oropharyngeal decontamination on the intestinal microbrota in ICU patients’ [1]. Benus tested the hypothesis that selective decontamination of the digestive tract (SDD) may achieve its claimed benefits by leaving the anaerobic intestinal microbiota unaffected, which indicates a misunderstanding of SDD [2]. SDD was designed based on the observation that critical illness changes flora. Critical illness promotes a shift from normal (S. pneumoniae in the throat and E. coli in the gut) towards abnormal carriage (aerobic Gram-negative bacilli and methicillin-resistant Staphylococcus aureus) and overgrowth of both. Parenteral cefotaxime controls overgrowth of ‘normal’ flora, whereas abnormal flora is controlled by enteral polymyxin/tobramycin. There are 60 randomised controlled trials (RCT) and 10 meta-analyses confirming that SDD reduces pneumonia (72%), septicaemia (37%) and mortality (29%) without resistance emerging. n nBenus’s article focuses on ‘selectivity’. Anaerobes rarely cause infections; instead, the indigenous anaerobic flora contributes to physiology and control of abnormal carriage, i.e. it promotes colonisation resistance (CR) [3]. Antimicrobials suppressing anaerobes are ‘non-selective’, those leaving them virtually intact are ‘selective’. n nUsing fluorescent in situ hybridization, Benus demonstrates that SDD impacts the indigenous flora, particularly Faecalibacterium prausnitzii, an anaerobic Gram-negative bacillus significantly reduced by high faecal tobramycin levels. They hypothesize that F. prausnitzii plays a role in maintaining CR, therefore SDD cannot be beneficial by leaving colonic microbiota unaffected. Interestingly, the faecal samples studied by Benus were collected from ICU patients enrolled in a recent RCT showing efficacy and safety of SDD [1]. n nThe only conclusion is that SDD is effective and safe although not selective, as described by Vollaard et al. [3]. Donskey [4] wrote that SDD has tremendous potential although it is not truly selective. n nSix healthy volunteers were challenged with cefotaxime-resistant Enterobacter cloacae after intravenous administration of cefotaxime [3]. All became carriers, five experienced overgrowth, and all cleared the strain during pre-treatment without cefotaxime. Parenteral cefotaxime was chosen for SDD [2] as it has been shown to control overgrowth of normal flora through its high salivary and biliary concentrations. These levels are also bactericidal against Clostridium species, Gram-positive bacilli amongst the indigenous anaerobes, and are thought to contribute to CR [5]. n nBenus assessed the impact of SDD on CR in 17 ICU patients and reports a significant reduction in F. prausnitzii, which is hypothesized to play a role in maintaining CR, in contrast to Wensinck who showed that CR is based on anaerobic Gram-positive Clostridium species. Hence, Benus concludes that SDD is not selective. n nBenus fails to acknowledge Vollaard’s and Donskey’s work, although both are relevant to the assertion that SDD is a contradiction in terms, i.e., effective decontamination or eradication of gut overgrowth whilst maintaining complete selectivity does not make sense. However, the originators of SDD have always been aware of this contradiction in terms [2] preferring effectivity over selectivity, if negative consequences of non-selectivity are neutralised by enteral antimicrobials (polymyxin/tobramycin/amphotericin B). n nIn conclusion, SDD exerts benefits via antimicrobial concentrations effective against overgrowth of normal and abnormal flora rather than by sparing the CR flora. The clinical impact of F. prausnitzii reduction in the critically ill is unclear.

Monitoring lung mechanics and airway pressures during differential lung ventilation (DLV) with emphasis on weaning from DLV

Fifteen polytrauma patients with asymmetric pulmonary contusion were treated with differential lung ventilation (DLV) for a mean of 106 hours (range 24–298, median 83). The differential time constant (Tc), compliance (Ct), inspiratory and expiratory airway resistance (Rawinsp, Rawexp) and peak-airway pressure (Pawpeak) were monitored to evaluate the function of each lung. Values measured after starting DLV were compared to those obtained prior to stopping DLV in order to analyse whether these parameters had returned to symmetrical values when recommencement of conventional mechanical ventilation was considered on clinical parameters and also whether these could be useful criteria for weaning from DLV. The significant difference in Tc of the contused lung compared to the contralateral lung after starting DLV is mainly determined by altered Ct resulting from contusion. During DLV improvement of Ct resulted in identical Tc of both lungs prior to stopping DLV. Changes in the Rawinsp contributed little to changes in Tc. Identical Tc prior to stopping DLV coincided with identical Pawpeak on symmetrical ventilator settings. These data suggest that when less advanced monitoring equipment is available, the differential Pawpeak might be used as a measure of differential lung mechanics in asymmetrical pulmonary contusion.

EFFICACY OF A HEAT AND MOISTURE EXCHANGE DEVICE DURING HIGH-FREQUENCY JET VENTILATION

A hygroscopic condensor humidifier has been tested during high-frequency jet ventilation, in an experimental set up. The influence of various ventilator settings on relative humidity, temperature and water content of the inspiratory and expiratory gases was investigated. The device provides adequate conditioning of the inspired gases with regard to relative humidity, temperature and water content at various ventilator settings.