Long-term use of selective decontamination of the digestive tract does not increase antibiotic resistance: a 5-year prospective cohort study

Purpose  

Despite the evidence, the use of selective decontamination of the digestive tract (SDD) remains controversial, largely because of concerns that it may promote the emergence of antibiotic-resistant strains. The purpose of this study was to evaluate the long-term incidence of carriage of antibiotic-resistant bacteria (ARB), its clinical impact on developing infections and to explore risk factors of acquiring resistance.     

Presence of tobramycin in blood and urine during selective decontamination of the digestive tract in critically ill patients,a prospective cohort study

Introduction  

Tobramycin is one of the components used for selective decontamination of the digestive tract (SDD), applied to prevent colonization and subsequent infections in critically ill patients. Tobramycin is administered in the oropharynx and gastrointestinal tract and is normally not absorbed. However, critical illness may convey gut barrier failure. The aim of the study was to assess the prevalence and amount of tobramycin leakage from the gut into the blood, to quantify tobramycin excretion in urine, and to determine the association of tobramycin leakage with markers of circulation, kidney function and other organ failure.     

Hypothermia,immune suppression and SDD: can we have our cake and eat it?

In vitro studies and clinical observations suggest that both accidental and controlled/therapeutic hypothermia have a strong immunosuppressive effect, and that hypothermia increases the risk of infections, especially wound infections and pneumonia. In the previous issue of Critical Care, Kamps and colleagues report that when hypothermia was used for prolonged periods in patients with severe traumatic brain injury in conjunction with selective decontamination of the digestive tract, the risks of infection were the same or lower in patients treated with therapeutic cooling. The risk of infection is widely regarded as the most important danger of therapeutic cooling. The findings of Kamps and colleagues need to be verified in prospective trials and in higher-resistance environments, but raise the possibility of cooling for prolonged periods with greatly reduced risk. We may be able to have our cake and eat it.     

Colistin resistance in gram-negative bacteria during prophylactic topical colistin use in intensive care units

Purpose

Topical use of colistin as part of selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) has been associated with improved patient outcome in intensive care units (ICU), yet little is known about the risks of colistin resistance. We quantified effects of selective decontamination on acquisition of colistin-resistant gram-negative bacteria (GNB) using data from a cluster-randomized study and a single-centre cohort.

Methods

Acquisition of colistin-resistant GNB and conversion from susceptible to resistance in GNB was determined in respiratory samples [from patients receiving SDD (n = 455), SOD (n = 476), or standard care (SC) (n = 315)], and in rectal swabs from 1,840 SDD-patients. Genotyping of converting isolates was performed where possible.

Results

The respiratory tract acquisition rates of colistin-resistant GNB were comparable during SDD, SOD, and SC and ranged from 0.7 to 1.1/1,000 patient-days at risk. Rectal acquisition rates during SDD were <3.3/1,000 days at risk. In patients with respiratory tract GNB carriage, conversion rates were 3.6 and 1.1/1,000 patient-days at risk during SDD and SC, respectively, (p > 0.05). In patients with rectal GNB carriage conversion rates during SDD were 5.4 and 3.2/1,000 days at risk and 15.5 and 12.6/1,000 days at risk when colonized with tobramycin-resistant GNB.

Conclusions

Acquisition rates with colistin-resistant GNB in the respiratory tract were low and comparable with and without topical use of colistin. Rates of acquisition of colistin-resistant GNB during SDD were—in ICUs with low endemicity of antibiotic resistance—<2.5/1,000 days at risk, but were fivefold higher during persistent GNB colonization and 15-fold higher during carriage with tobramycin-resistant GNB.     

A systematic review of therapeutic hypothermia for adult patients following traumatic brain injury

Introduction

Research into therapeutic hypothermia following traumatic brain injury has been characterised by small trials of poor methodological quality, producing variable results. The Cochrane review, published in 2009, now requires updating. The aim of this systematic review is to assess the effectiveness of the application of therapeutic hypothermia to reduce death and disability when administered to adult patients who have been admitted to hospital following traumatic brain injury.

Methods

Two authors extracted data from each trial. Unless stated in the trial report, relative risks and 95% confidence intervals (CIs) were calculated for each trial. We considered P < 0 · 05 to be statistically significant. We combined data from all trials to estimate the pooled risk ratio (RR) with 95% confidence intervals for death, unfavourable outcome, and pneumonia. All statistical analyses were performed using RevMan 5.1 (Cochrane IMS, Oxford, UK) and Stata (Intercooled Version 12.0, StataCorp LP). Pooled RRs were calculated using the Mantel-Haenszel estimator. The random effects model of DerSimonian and Laird was used to estimate variances for the Mantel-Haenszel and inverse variance estimators.

Results

Twenty studies are included in the review, while 18 provided mortality data. When the results of 18 trials that evaluated mortality as one of the outcomes were statistically aggregated, therapeutic hypothermia was associated with a significant reduction in mortality and a significant reduction in poor outcome. There was a lack of statistical evidence for an association between use of therapeutic hypothermia and increased onset of new pneumonia.

Conclusions

In contrast to previous reviews, this systematic review found some evidence to suggest that therapeutic hypothermia may be of benefit in the treatment of traumatic brain injury. The majority of trials were of low quality, with unclear allocation concealment. Low quality trials may overestimate the effectiveness of hypothermia treatment versus standard care. There remains a need for more, high quality, randomised control trials of therapeutic hypothermia after traumatic brain injury.PROSPERO Systematic Review Registration Number 2012: CRD42012002449.     

The effectiveness of early prophylactic hypothermia in adult patients with traumatic brain injury: A systematic review and meta-analysis

ObjectivesPreviously published systematic reviews have explored the effects of therapeutic hypothermia on adult patients with traumatic brain injury (TBI). However, none explored the effect of early prophylactic hypothermia (within 6 h from injury to hypothermia induction). Animal studies indicated that early prophylactic hypothermia may reduce secondary injury and improve neurological outcomes. This systematic review aimed to investigate the effects of early prophylactic hypothermia on adult TBI regarding mortality, favourable outcomes, and complications.Data sourceWe searched electronic databases including Cochrane CENTRAL, PubMed, MEDLINE, CINAHL, EMBASE, Web of Science, OpenGrey, and ClinicalTrials.gov from inception to June 12, 2019. Manual search was conducted for additional information.Review methodsOnly randomised controlled trials were included. The Cochrane Collaboration Risk of Bias Tool was used to assess the quality of included studies. We extracted general demographic characteristics, the initiation timing, methods of cooling, duration, target temperature, rewarming rate, mortality, neurological outcomes, and complications.ResultsSix studies with a total of 1207 participants were included. Meta-analyses showed no significant difference in mortality and favourable outcomes (risk ratio = 1.11, 95% confidence interval = 0.90–1.37, P = 0.32; risk ratio = 1.03, 95% confidence interval = 0.91–1.16, P = 0.65, respectively). Similar results were found regarding different durations of hypothermia and different rewarming rates. Various complications were reported in the included studies. No statistical difference was found in three studies, while complications were reported to be significantly higher in the hypothermia group in the other three studies.ConclusionsThis review does not support the use of early prophylactic hypothermia (within 6 h after injury) as a neurological protection strategy in adult patients with TBI, irrespective of the short term or long term. No significant benefits were found regarding hypothermia with different rewarming rates. Owing to the limited number of studies, more randomised controlled trials with higher quality are required to establish true effects of early hypothermia in adult TBI.     

The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest

Background

Brain injury is considered the main cause of death in patients who are hospitalized after cardiac arrest (CA). Induced hypothermia is recommended as neuroprotective treatment after (CA) but may affect prognostic parameters. We evaluated the effect of delayed neurological prognostication on the mode of death in hypothermia-treated CA-survivors.

Study design

Retrospective study at a Swedish university hospital, analyzing all in-hospital and out-of-hospital CA-patients treated with hypothermia during a 5-year period. Cause of death was categorized as brain injury, cardiac disorder or other. Multimodal neurological prognostication and decision on level of care was performed in comatose patients 72 h after rewarming. Neurological function was evaluated by Cerebral Performance Categories scale (CPC).

Results

Among 162 patients, 76 survived to hospital discharge, 65 of whom had a good neurological outcome (CPC 1–2), and 11 were severely disabled (CPC 3). No patient was in vegetative state. The cause of death was classified as brain injury in 61 patients, cardiac disorder in 14 and other in 11. Four patients were declared brain dead and became organ donors. They were significantly younger (median 40 years) and with long time to ROSC. Active intensive care was withdrawn in 50 patients based on a statement of poor neurological prognosis at least 72 h after rewarming. These patients died, mainly from respiratory complications, at a median 7 days after CA.

Conclusion

Following induced hypothermia and delayed neurological prognostication, brain injury remains the main cause of death after CA. Most patients with a poor prognosis statement died within 2 weeks.     

Pre-hospital cooling of patients following cardiac arrest is effective using even low volumes of cold saline

Introduction  

Pre-hospital induction of therapeutic mild hypothermia (TH) may reduce post-cardiac arrest brain injury in patients resuscitated from out-of-hospital cardiac arrest. Most often, it is induced by a rapid intravenous administration of as much as 30 ml/kg of cold crystalloids. We decided to assess the pre-hospital cooling effectivity of this approach by using a target dose of 15-20 ml/kg of 4°C cold normal saline in the setting of the physician-staffed Emergency Medical Service. The safety and impact on the clinical outcome have also been analyzed.     

Mild hypothermia in improving multiple organ dysfunction after cardiac arrest

BACKGROUND:

Resuscitation after cardiac arrest (CA) with a whole-body ischemia–reperfusion injury causes brain injury and multiple organ dysfunction (MODS). This study aimed to determine whether mild systemic hypothermia could decrease multiple organ dysfunctions after resuscitation from cardiac arrest.

METHODS:

The patients who had been resuscitated after cardiac arrest were reviewed. During the resuscitation they had been assigned to undergo therapeutic hypothermia (target temperature, 32°C to 34°C, measured in the rectum) over a period of 24 to 36 hours or to receive standard treatment with normothermia. Markers of different organ injury were evaluated for the first 72 hours after recovery of spontaneous circulation (ROSC).

RESULTS:

At 72 hours after ROSC, 23 patients in the hypothermia group for whom data were available had favorable neurologic, myocardial, hepatic and pulmonic outcomes as compared with 26 patients in the normothermia group. The values of renal function were not significantly different between the two groups. However, blood coagulation function was badly injured in the hypothermia group.

CONCLUSION:

In the patients who have been successfully resuscitated after cardiac arrest, therapeutic mild hypothermia can alleviate dysfunction after resuscitation from cardiac arrest.KEY WORDS: Cardiac arrest, Ischemia reperfusion injury, Mild hypothermia, Multiple organ dysfunction     

Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality

Purpose  

Selective decontamination of the digestive tract (SDD) has been shown to decrease the infection rate and mortality in intensive care units (ICUs); Lactobacillus plantarum 299/299v plus fibre (LAB) has been used for infection prevention and does not harbour the potential disadvantages of antibiotics. The objective was to assess whether LAB is not inferior to SDD in infection prevention.     

Mild hypothermia therapy reduces blood glucose and lactate and improves neurologic outcomes in patients with severe traumatic brain injury

Purpose

The study aimed to investigate the association between blood glucose or lactate and the outcomes of severe traumatic brain injury (TBI), and to evaluate the effect of mild hypothermia therapy on glucose and lactate levels.

Methods

Eighty-one patients with TBI were randomly divided into normothermia (n = 41) and mild hypothermia (n = 40) group. Body temperature of hypothermia group was maintained at 32.7°C for 72 hours. Arterial blood glucose and lactic acid were determined before and after hypothermia therapy. Glasgow Outcome Scale (GOS) score was assessed 3 months after the treatment.

Results

The mean glucose (7.04 ± 0.51 vs 9.71 ± 1.63 mmol/L, P < .05) in the hypothermia group was lower than in the normothermia group after hypothermia therapy. There were more patients with good neurologic function (GOS 4-5) in the hypothermia group than in the normothermia group (75.0% vs 51.2%, P = .038). Multivariate regression analysis showed that blood glucose greater than 10 mmol/L (adjusted risk ratio, 5.7; 95% confidence interval, 1.4-13.2; P < .05) was an independent predictor for poor neurologic outcomes in these patients, and hypothermia therapy was an independent predictor for favorable outcomes (risk ratio, 4.9; 95% confidence interval, 1.0-15.6; P < .05). No significant association between lactate and GOS scores was identified in the multivariate analysis.

Conclusion

Hyperglycemia after TBI was associated with poor clinical outcomes, but the predictive value of blood lactate level requires further investigation. Hypothermia therapy improves neurologic outcomes in patients with severe TBI, and reduction in blood glucose may be partially responsible for the improved outcomes.     

Decontamination of the digestive tract and oropharynx: hospital acquired infections after discharge from the intensive care unit

Objective  To determine the incidence rates of hospital acquired infections (HAI) during the first 14 days after ICU discharge after treatment during ICU-stay with Selective Decontamination of the Digestive tract (SDD), Selective Oropharyngeal Decontamination (SOD) or Standard Care (SC). Design  Prospective observational study. Setting  ICUs in two tertiary care hospitals. Patients  Patients discharged from the ICU to the ward. Interventions  None. Measurements and results  Post-ICU incidences of HAI per 1,000 days at risk were 11.2, 12.9 and 8.3 for patients that had received SDD (n = 296), SOD (n = 286) or SC (n = 289) respectively in ICU, yielding relative risks, as compared to SC, of 1.49 (CI₉₅ 0.9–2.47) for SOD and 1.44 (CI₉₅ 0.87–2.39) for SDD. Incidences of surgical site infections (per 100 surgical procedures) were 4 after SC and 11.8 and 8 after SOD and SDD (p = 0.04). Among patients that succumbed in the hospital after ICU-stay (n = 58) eight (14%) had developed HAI after ICU discharge; 3 of 21 after SDD, 3 of 15 after SOD and 2 of 22 after SC. Conclusions  Incidences of HAI in general wards tended to be higher in patients that had received either SDD or SOD during ICU-stay, but it seems unlikely that these infections have an effect on hospital mortality rates.     

Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest

Introduction  

Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome.     

Impact of digestive and oropharyngeal decontamination on the intestinal microbiota in ICU patients

Purpose

Selective digestive microbial decontamination (SDD) is hypothesized to benefit patients in intensive care (ICU) by suppressing Gram-negative potential pathogens from the colon without affecting the anaerobic intestinal microbiota. The purpose of this study was to provide more insight to the effects of digestive tract and oropharyngeal decontamination on the intestinal microbiota by means of a prospective clinical trial in which faecal samples were collected from ICU patients for intestinal microbiota analysis.

Methods

The faecal samples were collected from ICU patients enrolled in a multicentre trial to study the outcome of SDD and selective oral decontamination (SOD) in comparison with standard care (SC). Fluorescent in situ hybridization (FISH) was used to analyze the faecal microbiota. The numbers of bacteria from different bacterial groups were compared between the three regimens.

Results

The total counts of bacteria per gram faeces did not differ between regimens. The F. prausnitzii group of bacteria, representing an important group among intestinal microbiota, was significantly reduced in the SDD regimen compared to the SC and SOD. The Enterobacteriaceae were significantly suppressed during SDD compared to both SOD and SC; enterococci increased in SDD compared to both other regimens.

Conclusions

The composition of the intestinal microbiota is importantly affected by SDD. The F. prausnitzii group was significantly suppressed during SDD. This group of microbiota is a predominant producer of butyrate, the main energy source for colonocytes. Reduction of this microbiota is an important trade-off while reducing gram-negative bacteria by SDD.     

A Case of Commotio Cordis Treated with Therapeutic Hypothermia

Background

Therapeutic hypothermia is used as a neuroprotective strategy for patients who have persistent neurologic compromise after return of spontaneous circulation from cardiac arrest. The 2010 American Heart Association Guidelines recommend the use of therapeutic hypothermia in adult cardiac arrest patients when the initial rhythm is ventricular fibrillation. These recommendations are based on primary research in patients with a cardiac cause of their ventricular fibrillation.

Case Report

A 43-year-old male was brought to our emergency department (ED) with commotio cordis. He was struck in the chest with a baseball bat, after which he collapsed at the scene and was pulseless. Return of spontaneous circulation was achieved after defibrillation by treating paramedics, and the patient remained comatose on arrival to the ED. He was transferred to the intensive care unit and treated with therapeutic hypothermia at target temperature of 32−34°C. He was extubated on day 3, and discharged home on day 8 with good neurologic function.

Why Should An Emergency Physician Be Aware of This?

We report a case of commotio cordis in which the adult patient was treated with therapeutic hypothermia and had a favorable outcome. To our knowledge, this is the first reported case of its kind. Evidence for the use of therapeutic hypothermia is incomplete in patients with a traumatic cause of cardiac arrest, such as commotio cordis, despite probable similarities in the pathophysiology of anoxic brain injury. Our case illustrates that there may be benefit from use of therapeutic hypothermia for a broader population than is currently recommended.     

Selective decontamination of the digestive tract: the mechanism of action is control of gut overgrowth

Purpose

Gut overgrowth is the pathophysiological event in the critically ill requiring intensive care. In relation to the risk of developing a clinically important outcome, gut overgrowth is defined as?≥10⁵ potential pathogens including ‘abnormal’ aerobic Gram-negative bacilli (AGNB), ‘normal’ bacteria and yeasts, per mL of digestive tract secretion. Surveillance samples of throat and gut are the only samples to detect overgrowth. Gut overgrowth is the crucial event which precedes both primary and secondary endogenous infection, and a risk factor for the development of de novo resistance. Selective decontamination of the digestive tract (SDD) is an antimicrobial prophylaxis designed to control overgrowth.

Methods

There have been 65 randomised controlled trials of SDD in 15,000 patients over 25?years and 11 meta-analyses, which are reviewed.

Results and conclusions

These trials demonstrate that the full SDD regimen using parenteral and enteral antimicrobials reduces lower airway infection by 72?%, blood stream infection by 37?%, and mortality by 29?%. Resistance is also controlled. Parenteral cefotaxime which reaches high salivary and biliary concentrations eradicates overgrowth of ‘normal’ bacteria such as Staphylococcus aureus in the throat. Enteral polyenes control ‘normal’ Candida species. Enteral polymyxin and tobramycin, eradicate, or prevent gut overgrowth of ‘abnormal’ AGNB. Enteral vancomycin controls overgrowth of ‘abnormal’ methicillin-resistant S. aureus. SDD controls overgrowth by achieving high antimicrobial concentrations effective against ‘normal’ and ‘abnormal’ potential pathogens rather than by selectivity.     

Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study

Introduction

Colonisation of the lower respiratory tract with Candida species occurs in 25% of mechanically ventilated critically ill patients, and is associated with increased morbidity. Nebulised amphotericin B has been used to eradicate Candida as part of selective decontamination of the digestive tract (SDD) protocols, but its effectiveness is unknown. We aimed to determine the effectiveness of nebulised amphotericin B in eradicating Candida respiratory tract colonisation in patients receiving SDD.

Methods

We included consecutive mechanically ventilated patients during a four-year period. Microbiological screening was performed upon admission and twice weekly thereafter according to a standardised protocol. A colonisation episode was defined as the presence of Candida species in two consecutive sputum samples taken at least one day apart. To correct for time-varying bias and possible confounding, we used a multistate approach and performed time-varying Cox regression with adjustment for age, disease severity, Candida load at baseline and concurrent corticosteroid use.

Results

Among 1,819 patients, colonisation with Candida occurred 401 times in 363 patients; 333 of these events were included for analysis. Decolonisation occurred in 51 of 59 episodes (86%) and in 170 of 274 episodes (62%) in patients receiving and not receiving nebulised amphotericin B, respectively. Nebulised amphotericin B was associated with an increased rate of Candida eradication (crude HR 2.0; 95% CI 1.4 to 2.7, adjusted HR 2.2; 95% CI 1.6 to 3.0). Median times to decolonisation were six and nine days, respectively. The incidence rate of ventilator-associated pneumonia, length of stay and mortality did not differ between both groups.

Conclusions

Nebulised amphotericin B reduces the duration of Candida colonisation in the lower respiratory tracts of mechanically ventilated critically ill patients receiving SDD, but data remain lacking that this is associated with a meaningful improvement in clinical outcomes. Until more evidence becomes available, nebulised amphotericin B should not be used routinely as part of the SDD protocol.     

Rationale,methodology, and implementation of a nationwide multicenter randomized controlled trial of long-term mild hypothermia for severe traumatic brain injury (the LTH-1 trial)

BackgroundTraumatic brain injury (TBI) is a major public health problem recently, however, no intervention showing convincing efficacy. Therapeutic hypothermia with a relatively long duration (more than 48 h), as a promising treatment measure, might improve the patient outcome following severe TBI.Methods/designThe LTH-1 trial is a prospective, nationwide multicenter, randomized, controlled clinical trial to examine the efficacy and safety of long-term mild hypothermia in adult patients after severe traumatic brain injury. A total of 300 consecutive patients will be recruited from 15 large neurosurgical centers in China. The eligible patient will be randomized to receive either long-term mild hypothermia (34–35 °C) for 5 days, or normothermia (36–37 °C). Additionally, a standardized management protocol will be used in all patients. The primary end point is the neurological outcome 6 months post-injury on the Glasgow Outcome Scale. The secondary outcomes include GOS score at one month post-injury, mortality during six months after injury, length of ICU and hospital stay, intracranial pressure control and Glasgow Coma Scale score during the hospital stay and frequency of complications during the six-month follow-up period.DiscussionLong-term hypothermia is recommended by most recent studies and its efficacy urgently needs to be established in randomized controlled settings. The LTH-1 trial, together with other ongoing studies, will present more evidence for optimal use of hypothermia in severe TBI patients.     

Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort

Objective

Brain injury is well established as a cause of early mortality after out-of-hospital cardiac arrest (OHCA), but postresuscitation shock also contributes to these deaths. This study aims to describe the respective incidence, risk factors, and relation to mortality of post-cardiac arrest (CA) shock and brain injury.

Design

Retrospective analysis of an observational cohort.

Setting

24-bed medical intensive care unit (ICU) in a French university hospital.

Patients

All consecutive patients admitted following OHCA were considered for analysis. Post-CA shock was defined as a need for infusion of vasoactive drugs after resuscitation. Death related to brain injury included brain death and care withdrawal for poor neurological evolution.

Intervention

None.

Measurements and main results

Between 2000 and 2009, 1,152 patients were admitted after OHCA. Post-CA shock occurred in 789 (68 %) patients. Independent factors associated with its onset were high blood lactate and creatinine levels at ICU admission. During the ICU stay, 269 (34.8 %) patients died from post-CA shock and 499 (65.2 %) from neurological injury. Age, raised blood lactate and creatinine values, and time from collapse to restoration of spontaneous circulation increased the risk of ICU mortality from both shock and brain injury, whereas a shockable rhythm was associated with reduced risk of death from these causes. Finally, bystander cardiopulmonary resuscitation (CPR) decreased the risk of death from neurological injury.

Conclusions

Brain injury accounts for the majority of deaths, but post-CA shock affects more than two-thirds of OHCA patients. Mortality from post-CA shock and brain injury share similar risk factors, which are related to the quality of the rescue process.