Bastiaan Hj Wittekamp

Clinical review: Post-extubation laryngeal edema and extubation failure in critically ill adult patients

Laryngeal edema is a frequent complication of intubation. It often presents shortly after extubation as post-extubation stridor and results from damage to the mucosa of the larynx. Mucosal damage is caused by pressure and ischemia resulting in an inflammatory response. Laryngeal edema may compromise the airway necessitating reintubation. Several studies show that a positive cuff leak test combined with the presence of risk factors can identify patients with increased risk for laryngeal edema. Meta-analyses show that pre-emptive administration of a multiple-dose regimen of glucocorticosteroids can reduce the incidence of laryngeal edema and subsequent reintubation. If post-extubation edema occurs this may necessitate medical intervention. Parenteral administration of corticosteroids, epinephrine nebulization and inhalation of a helium/oxygen mixture are potentially effective, although this has not been confirmed by randomized controlled trials. The use of non-invasive positive pressure ventilation is not indicated since this will delay reintubation. Reintubation should be considered early after onset of laryngeal edema to adequately secure an airway. Reintubation leads to increased cost, morbidity and mortality.

Postextubation laryngeal edema and stridor resulting in respiratory failure in critically ill adult patients: updated review.

Endotracheal intubation is frequently complicated by laryngeal edema, which may present as postextubation stridor or respiratory difficulty or both. Ultimately, postextubation laryngeal edema may result in respiratory failure with subsequent reintubation. Risk factors for postextubation laryngeal edema include female gender, large tube size, and prolonged intubation. Although patients at low risk for postextubation respiratory insufficiency due to laryngeal edema can be identified by the cuff leak test or laryngeal ultrasound, no reliable test for the identification of high-risk patients is currently available. If applied in a timely manner, intravenous or nebulized corticosteroids can prevent postextubation laryngeal edema; however, the inability to identify high-risk patients prevents the targeted pretreatment of these patients. Therefore, the decision to start corticosteroids should be made on an individual basis and on the basis of the outcome of the cuff leak test and additional risk factors. The preferential treatment of postextubation laryngeal edema consists of intravenous or nebulized corticosteroids combined with nebulized epinephrine, although no data on the optimal treatment algorithm are available. In the presence of respiratory failure, reintubation should be performed without delay. Application of noninvasive ventilation or inhalation of a helium/oxygen mixture is not indicated since it does not improve outcome and increases the delay to intubation.

Antibiotic prophylaxis in the era of multidrug-resistant bacteria

The prophylactic use of antibiotics can only be justified when clinical benefits on relevant patient outcomes, such as morbidity or mortality, cost-effectiveness, and absence of immediate emergence of antibiotic resistance have been unequivocally demonstrated. In some intensive care unit (ICU) patients, antibiotic prophylaxis is used as part of selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD). Recent trials in ICUs with low levels of antibiotic resistance strongly suggest that both regimens reduce the incidence of ICU-acquired infections and improve patient survival. Naturally, the unique microbial ecology of such settings reduce generalizability of results. Therefore, the routine use of SOD and SDD remains highly controversial, especially in ICUs with higher levels of antibiotic resistance. Moreover, convincing evidence is still missing on several important aspects related to efficacy and safety. Despite numerous trials, effects of SDD and SOD on antibiotic resistance during and after decolonization treatment have still been insufficiently investigated, and existing results are contradicting. Furthermore, the effects of both regimens on the non-culturable part of the intestinal flora remain unknown. Finally, cost-effectiveness has not been thoroughly investigated, and prices of the antimicrobial agents that have been used have increased dramatically in recent years. In this review, important knowledge gaps that so far prevent the widespread use of SDD and SOD will be addressed.

Catheter-related bloodstream infections: a prospective observational study of central venous and arterial catheters

Abstract Background: Catheter-related bloodstream infections (CRBSIs) can lead to increased morbidity and length of stay (LOS) in the intensive care unit (ICU). The purpose of this study was to analyse the incidence of catheter-related bloodstream infection associated with central venous catheters (CVCs) and arterial catheters (ACs) and to identify risk factors for CRBSIs in our ICU. Methods: This was a prospective observational study in a 17-bed medical–surgical ICU of a 715-bed university hospital. Patients admitted to the ICU for ≥ 24 h between 1 September 2007 and 30 April 2008, who received a CVC or AC, were included in the study. Results: A total of 219 patients with 258 CVCs and 336 ACs were included in the study and observed for a combined total of 3172 catheter-days. The CRBSI incidence density was 1.2 per 1000 catheter-days for CVCs and 2.1 per 1000 catheter-days for ACs. The mean LOS (p = 0.003), the number of days a catheter remained in situ (p = 0.001), and the length of pre-ICU in-hospital stay (p = 0.031) were significantly higher in the CRBSI group. Risk factor analysis was not reliable due to the low number of CRBSIs. Conclusion: The incidence of AC- and CVC-related CRBSIs was comparable to the incidence reported in the literature. However, the incidence for ACs was higher than for CVCs. In addition to CVCs, ACs should be considered a possible cause of catheter-related infections and both should be replaced when CRBSI is suspected.

Selective decontamination in European intensive care patients

Selective decontamination of the digestive tract (SDD) is both one of the most studied and one of the most debated preventive measures for critically ill patients in intensive care units (ICUs) (see box). After the first trials in hematology patients in the 1970s [1, 2], the concept was introduced in ICU populations in the 1980s [3], and frequently studied in the following decade [4]. Various different regimens were studied, including strictly oropharyngeal decontamination [selective oropharyngeal decontamination (SOD)] (see box). At the turn of the century there were more than 50 randomized, though mostly small and single-center, trials and several meta-analyses. The summarized conclusions from these studies were that SDD was associated with reductions of respiratory tract infections in ICUs with low levels of antibiotic resistance, but that improvement of patient outcome (i.e., better ICU survival) could be demonstrated in meta-analyses only [5, 6]. Since that time, numbers of new SDD studies declined and this measure was not widely adopted in European ICUs, mainly because the evidence for better patient outcome was considered not convincing, and because of the unknown—possibly detrimental—effects of prophylactic antibiotic use on antibiotic resistance development. The Netherlands became the exception to this rule, due to two studies, both demonstrating survival benefits of patients receiving SDD [7, 8]. In both studies, SDD was used as a unit-wide intervention in ICUs with low prevalence of antibiotic-resistant bacteria, and in both studies SDD was associated with lower, instead of higher, rates of antibiotic resistance. However, the absolute 28-day mortality reduction in the largest study was 3.5% (relative reduction was 13%) and only determinable in a random-effects logistic regression model with adjustment for baseline differences between study groups [8]. Moreover, in the latter study, SDD was equally effective in improving patient outcome as SOD. The beneficial results of SDD and SOD obtained in Dutch ICUs raise the question of whether both measures could be equally beneficial in other European countries. Here, we address some methodological issues relevant to future attempts to quantify the effects of SDD or SOD in critically ill patients.

Associations Between Enteral Colonization With Gram-Negative Bacteria and Intensive Care Unit–Acquired Infections and Colonization of the Respiratory Tract

Background Enteral and respiratory tract colonization with gram-negative bacteria may lead to subsequent infections in critically ill patients. We aimed to clarify the interdependence between gut and respiratory tract colonization and their associations with intensive care unit (ICU)-acquired infections in patients receiving selective digestive tract decontamination (SDD). Methods Colonization status of the rectum and respiratory tract was determined using twice-weekly microbiological surveillance in mechanically ventilated subjects receiving SDD between May 2011 and June 2015 in a tertiary medical-surgical ICU in the Netherlands. Acquisition of infections was monitored daily by dedicated observers. Marginal structural models were used to determine the associations between gram-negative rectal colonization and respiratory tract colonization, ICU-acquired gram-negative infection, and ICU-acquired gram-negative bacteremia. Results Among 2066 ICU admissions, 1157 (56.0%) ever had documented gram-negative carriage in the rectum during ICU stay. Cumulative incidences of ICU-acquired gram-negative infection and bacteremia were 6.0% (n = 124) and 2.1% (n = 44), respectively. Rectal colonization was an independent risk factor for both respiratory tract colonization (cause-specific hazard ratio [CSHR], 2.93 [95% confidence interval {CI}, 2.02-4.23]) and new gram-negative infection in the ICU (CSHR, 3.04 [95% CI, 1.99-4.65]). Both rectal and respiratory tract colonization were associated with bacteremia (CSHR, 7.37 [95% CI, 3.25-16.68] and 2.56 [95% CI, 1.09-6.03], respectively). Similar associations were observed when Enterobacteriaceae and glucose nonfermenting gram-negative bacteria were analyzed separately. Conclusions Gram-negative rectal colonization tends to be stronger associated with subsequent ICU-acquired gram-negative infections than gram-negative respiratory tract colonization. Gram-negative rectal colonization seems hardly associated with subsequent ICU-acquired gram-negative respiratory tract colonization.

Fighting antibiotic resistance in the intensive care unit using antibiotics

Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.

Nystatin versus amphotericin B to prevent and eradicate Candida colonization during selective digestive tract decontamination in critically ill patients

Dear Editor, Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) aim to eliminate potential pathogenic microorganisms, such as Gram-negative bacteria and yeasts, from the oropharynx and digestive tract of intensive care unit (ICU) patients [1–3]. Amphotericin B is mostly used as the antifungal component in SOD and SDD, but is increasingly difficult to acquire due to scarcity of raw materials and is also becoming increasingly expensive. Nystatin is a potential substitute as it is also effective against a broad range of fungi and not absorbed from the digestive tract [4]. However, the effects of both agents on Candida colonization and eradication in SDD have never been compared. We performed a before–after study evaluating two subsequent changes in SDD in a 32-bed medical-surgical ICU in the Netherlands. All patients admitted for 48 h or longer (i.e., eligible to receive SDD until discharge from the ICU) and who did not receive systemic antifungal therapy were included in the analysis. The local ethics committee waived the need for informed consent. There were three study periods (Table S1): period 1 (16 months), SDD treatment included (q.d.s.) application of a mouth paste containing 2 % polymyxin E, 2 % tobramycin and 2 % amphotericin B, administration (q.d.s) of a suspension with the same components (100 mg polymyxin E, 80 mg tobramycin and 500 mg amphotericin B) through the nasogastric tube, and the systemic administration (q.d.s.) of cefotaxime during the first 4 days of ICU admission (Am/Am); period 2 (17 months), nystatin (2 9 10^6 units per dose) replaced amphotericin B in the enteral solution only (Am/Nys); period 3 (10 months), nystatin replaced amphotericin B in both the oropharyngeal paste and enteral solution (Nys/Nys). From 1468 patients at least two rectum surveillance cultures were available, 1095 (75 %) were not colonized at the start of ICU admission and Candida acquisition in the rectum was analyzed. Patients’ characteristics are on Table S2. Compared to the reference period (i.e., Am/Am) and after adjustment for baseline imbalances in a Cox regression analysis,

Decontamination Strategies and Bloodstream Infections With Antibiotic-Resistant Microorganisms in Ventilated Patients: A Randomized Clinical Trial

Importance The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown. Objective To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance. Design, Setting, and Participants Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum &bgr;-lactamase–producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017. Interventions Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily. Main Outcomes and Measures The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period. Results A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, −0.6% to 1.1%), 0.6% (95% CI, −0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline. Conclusions and Relevance Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care. Trial Registration ClinicalTrials.gov Identifier: NCT02208154

Regulatory obstacles affecting ecological studies in the ICU

www.thelancet.com/infection Vol 14 October 2014 913 See Online for appendix and control measures in health-care facilities including King Fahd General Hospital, Jeddah, where substantial health-care–associated transmission of MERS-CoV between patients and staff happened, mainly due to overcrowding of patients by about four to fi ve times its maximum capacity in the emergency room. Overfl ow patients in the emergency room were relocated to other hospitals in Jeddah to reduce the risk of further transmission of the virus. Intensive education and training of staff about essential infection control measures were done to abort transmission of MERSCoV in health-care settings. The MOH has also invited experts from WHO and the US Centers for Disease Control and Prevention (CDC) to assess the outbreak. The advisory council, in collaboration with the CDC, has initiated case-control studies to identify risk factors for acquisition of MERS-CoV infection in primary and secondary cases. As new clinical information became available, a revision of the MERS-CoV case defi nition seemed appropriate. The new case defi nition (appendix) was developed based on reported health-care-associated MERS-CoV pneumonia (added as category 2 in the new case defi nition) and non-respiratory characteristics of patients with confi rmed infection who fi rst presented with acute febrile dengue-like illness with body aches, leucopenia, and thrombocytopenia (added as category 3). The new case defi nition added a fourth category for contacts of people with MERS-CoV who present with not only lower respiratory tract but also isolated upper respiratory tract features. This defi nition classifi ed the status of patients into three categories of suspect, probable, or confi rmed infection. The new MERS-CoV case defi nition was revised and approved by the advisory council after seeking external CDC expert opinion. An algorithm for MERS-CoV case management was developed (fi gure). According to this algorithm, patients with confi rmed MERS-CoV who have no evidence of pneumonia or who recover from pneu monia but remain positive for MERS-CoV, can be isolated at home after careful assessment of the home situation and suitability for isolation by the treating physician, highly trained social workers, or other health-care professionals by telephone or home visits. The CDC has released recommendations on how to assess the home situation and the advice to be given to patients on home isolation and his or her caregivers and household members, and also released guidance for the public, clinicians, and public-health authorities in the USA on control of the MERS-CoV infection.