Leptin levels in SARS-CoV-2 infection related respiratory failure: A cross-sectional study and a pathophysiological framework on the role of fat tissue.

Obesity is a risk factor for SARS-CoV-2 infected patients to develop respiratory failure. Leptin produced in visceral fat might play a role in the deterioration to mechanical ventilation. A cross sectional study was performed. The mean BMI was 31 kg/m2 (range 24.8-48.4) for the 31 SARS-CoV-2 ventilated patients and 26 kg/m2 (range 22.4-33.5) for 8 critically ill non-infected control patients. SARS-CoV-2 infected patients with a similar BMI as control patients appear to have significantly higher levels of serum leptin. The mean leptin level was 21.2 (6.0-85.2) vs 5.6 (2.4-8.2) ug/L for SARS-CoV-2 and controls respectively (p = 0.0007). With these findings we describe a clinical and biological framework that may explain these clinical observations. The ACE2 utilization by the virus leads to local pulmonary inflammation due to ACE2-ATII disbalance. This might be enhanced by an increase in leptin production induced by SARS-CoV-2 infection of visceral fat. Leptin receptors in the lungs are now more activated to enhance local pulmonary inflammation. This adds to the pre-existent chronic inflammation in obese patients. Visceral fat, lung tissue and leptin production play an interconnecting role. This insight can lead the way to further research and treatment.

Impact of Oral Chlorhexidine on Bloodstream Infection in Critically Ill Patients: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Oropharyngeal overgrowth of microorganisms in the critically ill is a risk factor for lower respiratory tract infection and subsequent invasion of the bloodstream. Oral chlorhexidine has been used to prevent pneumonia, but its effect on bloodstream infection never has been assessed in meta-analyses. The authors explored the effect of oral chlorhexidine on the incidence of bloodstream infection, the causative microorganism, and on all-cause mortality in critically ill patients. DESIGN: Systematic review and meta-analysis of published studies. SETTING: Intensive care unit. PARTICIPANTS: The study comprised critically ill patients receiving oral chlorhexidine (test group) and placebo or standard oral care (control group). INTERVENTIONS: PubMed and the Cochrane Register of Controlled Trials were searched. Odds ratios (ORs) were pooled using the random-effects model. MEASUREMENTS AND MAIN RESULTS: Five studies including 1,655 patients (832 chlorhexidine and 823 control patients) were identified. The majority of information was from studies at low or unclear risk bias; 1 study was at high risk of bias. Bloodstream infection and mortality were not reduced significantly by chlorhexidine (OR 0.74; 95% confidence interval [CI] 0.37-1.50 and OR 0.69; 95% CI 0.31-1.53, respectively). In the subgroup of surgical, mainly cardiac, patients, chlorhexidine reduced bloodstream infection (OR 0.47; 95% CI 0.22-0.97). Chlorhexidine did not affect any microorganism significantly. CONCLUSION: In critically ill patients, oropharyngeal chlorhexidine did not reduce bloodstream infection and mortality significantly and did not affect any microorganism involved. The presence of a high risk of bias in 1 study and unclear risk of bias in others may have affected the robustness of these findings.

Testing a conceptual model on early opening of the microcirculation in severe sepsis and septic shock: a randomised controlled pilot study.

BACKGROUND: Organ failure in severe sepsis and septic shock may be caused by microcirculatory failure. OBJECTIVE: The objective of this study is to test a conceptual model of microcirculatory failure by using a resuscitation strategy targeting early opening of the constricted microcirculation with active vasodilatation. DESIGN: A randomised controlled pilot study. SETTING: Single-centre mixed medical and surgical tertiary ICU. PATIENTS: Ninety severe sepsis and septic shock patients randomised to early opening microcirculation resuscitation group or standard resuscitation group. INTERVENTIONS: Standard resuscitation group: fluids, noradrenaline, dobutamine and hydrocortisone were given to achieve a mean arterial pressure (MAP) of more than 60 mmHg, cardiac index more than 2.5 l min m and ScvO2 more than 70%. Microcirculation resuscitation group: nitroglycerin, enoximone, dopamine and dexamethasone targeting a microvascular flow index (MFI), measured by sublingual side-stream dark field imaging, more than 2.5. MAIN OUTCOME MEASURE: A decrease in organ failure score (SOFA) on day four of ICU treatment. RESULTS: Data from 37 microcirculation resuscitation and 28 standard resuscitation patients were analysed. In the microcirculation resuscitation group, MFI of more than 2.5 was achieved after a mean ±â€ŠSD of 7.0 ±â€Š4.6 h. The microcirculation resuscitation group received more fluids, and noradrenaline was equally prescribed in both groups. Per protocol, the decrease in SOFA score at day 4 was not different between groups (P = 0.64). There was a significant reduction in SOFA score in both groups compared with admission (1.2 and 1.6 in microcirculation resuscitation and standard resuscitation groups, respectively; P = 0.028 and P = 0.045). CONCLUSION: Early opening of the microcirculation in patients with severe sepsis and septic shock using nitroglycerin, enoximone, dopamine and corticosteroids did not result in a faster reduction in organ failure than standard resuscitation. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00484133.

Acute posthypoxic myoclonus after cardiopulmonary resuscitation.

BACKGROUND: Acute posthypoxic myoclonus (PHM) can occur in patients admitted after cardiopulmonary resuscitation (CPR) and is considered to have a poor prognosis. The origin can be cortical and/or subcortical and this might be an important determinant for treatment options and prognosis. The aim of the study was to investigate whether acute PHM originates from cortical or subcortical structures, using somatosensory evoked potential (SEP) and electroencephalogram (EEG). METHODS: Patients with acute PHM (focal myoclonus or status myoclonus) within 72 hours after CPR were retrospectively selected from a multicenter cohort study. All patients were treated with hypothermia. Criteria for cortical origin of the myoclonus were: giant SEP potentials; or epileptic activity, status epilepticus, or generalized periodic discharges on the EEG (no back-averaging was used). Good outcome was defined as good recovery or moderate disability after 6 months. RESULTS: Acute PHM was reported in 79/391 patients (20%). SEPs were available in 51/79 patients and in 27 of them (53%) N20 potentials were present. Giant potentials were seen in 3 patients. EEGs were available in 36/79 patients with 23/36 (64%) patients fulfilling criteria for a cortical origin. Nine patients (12%) had a good outcome. A broad variety of drugs was used for treatment. CONCLUSIONS: The results of this study show that acute PHM originates from subcortical, as well as cortical structures. Outcome of patients admitted after CPR who develop acute PHM in this cohort was better than previously reported in literature. The broad variety of drugs used for treatment shows the existing uncertainty about optimal treatment.

Prognosis of coma after therapeutic hypothermia: a prospective cohort study.

OBJECTIVE: This study was designed to establish the reliability of neurologic examination, neuron-specific enolase (NSE), and median nerve somatosensory-evoked potentials (SEPs) to predict poor outcome in patients treated with mild hypothermia after cardiopulmonary resuscitation (CPR). METHODS: This multicenter prospective cohort study included adult comatose patients admitted to the intensive care unit (ICU) after CPR and treated with hypothermia (32-34°C). False-positive rates (FPRs 1 - specificity) with their 95% confidence intervals (CIs) were calculated for pupillary light responses, corneal reflexes, and motor scores 72 hours after CPR; NSE levels at admission, 12 hours after reaching target temperature, and 36 hours and 48 hours after collapse; and SEPs during hypothermia and after rewarming. The primary outcome was poor outcome, defined as death, vegetative state, or severe disability (Glasgow Outcome Scale 1-3) after 6 months. RESULTS: Of 391 patients included, 53% had a poor outcome. Absent pupillary light responses (FPR 1; 95% CI, 0-7) or absent corneal reflexes (FPR 4; 95% CI, 1-13) 72 hours after CPR, and absent SEPs during hypothermia (FPR 3; 95% CI, 1-7) and after rewarming (FPR 0; 95% CI, 0-18) were reliable predictors. Motor scores 72 hours after CPR (FPR 10; 95% CI, 6-16) and NSE levels were not. INTERPRETATION: In patients with persisting coma after CPR and therapeutic hypothermia, use of motor score or NSE, as recommended in current guidelines, could possibly lead to inappropriate withdrawal of treatment. Poor outcomes can reliably be predicted by testing brainstem reflexes 72 hours after CPR and performing SEP.

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. METHODS: This was a prospective observational cohort study. The setting was the 20-bed closed format-mixed ICU of a teaching hospital. The study population was critically ill patients with an expected stay of more than two days, receiving SDD with tobramycin, polymyxin-E and amphotericin-B four times daily in the oropharynx and stomach. Tobramycin concentration was measured in serum (sensitive high performance liquid chromatography - mass spectrometry/mass spectrometry (HLPC-MS/MS) assay) and 24-hour urine (conventional immunoassay), in 34 patients, 24 hours after ICU admission, and in 71 patients, once daily for 7 days. Tobramycin leakage was defined as tobramycin detected in serum at least once (> 0.05 mg/L). Ototoxicity was not monitored. RESULTS: Of the 100 patients with available blood samples, 83 had tobramycin leakage. Median highest serum concentration for each patient was 0.12 mg/L; 99% of the patients had at least one positive urinary sample (> 0.5 mg/L), 49% had a urinary concentration ≥ 1 mg/L. The highest tobramycin serum concentration was significantly associated with vasopressor support, renal and hepatic dysfunction, and C-reactive protein. At binary logistic regression analysis, high dopamine dose and low urinary output on Day 1 were the significant predictors of tobramycin leakage. Nephrotoxicity could not be shown. CONCLUSIONS: The majority of acute critically ill patients treated with enteral tobramycin as a component of SDD had traces of tobramycin in the blood, especially those with severe shock, inflammation and subsequent acute kidney injury, suggesting loss of gut barrier and decreased renal removal. Unexpectedly, urinary tobramycin was above the therapeutic trough level in half of the patients. Nephrotoxicity could not be demonstrated.

Selective digestive tract decontamination decreases time on ventilator in Guillain-Barré syndrome.

BACKGROUND: Ventilator-associated pneumonia (VAP) occurs in more than half of mechanically ventilated patients with Guillain-Barré syndrome (GBS) and is associated with prolonged mechanical ventilation (MV). We investigated the impact of selective decontamination of the digestive tract (SDD), an intervention that reduces hospital acquired infections in ICU patients, on duration of MV in GBS and neurological outcome at 6 months. METHODS: We performed a retrospective study in mechanically ventilated GBS patients in the Netherlands. We compared patients treated with and without SDD. Main outcomes were duration of MV and the ability to walk independently at 6 months. Statistical comparison was done with logistic and ordinal regression analyses. RESULTS: We included 124 GBS patients on MV at 2 weeks after first symptoms (SDD, n = 54 and non-SDD, n = 70). The median duration of MV without SDD was 42 days (interquartile range, IQR 25-77 days) versus 29 days with SDD (IQR 17-45 days). Median duration of MV for all included patients was 35 days. The adjusted odds ratio (OR) for duration of MV > 35 days in the SDD versus the non-SDD cohort was 0.37 (95% CI 0.17-0.77). SDD did not affect neurological recovery after 6 months from first symptoms. VAP occurred in 12% (95% CI 2-22%) in the SDD cohort and in 47% (95% CI 35-59%) in the non-SDD cohort. CONCLUSIONS: SDD in mechanically ventilated GBS patients reduced the time on the ventilator, probably by preventing VAP, but did not affect neurological recovery after 6 months.

Mean glucose during ICU admission is related to mortality by a U-shaped curve in surgical and medical patients: a retrospective cohort study.

INTRODUCTION: Lowering of hyperglycemia in the intensive care unit (ICU) is widely practiced. We investigated in which way glucose regulation, defined as mean glucose concentration during admission, is associated with ICU mortality in a medical and a surgical cohort. METHODS: Retrospective database cohort study including patients admitted between January 2004 and December 2007 in a 20-bed medical/surgical ICU in a teaching hospital. Hyperglycemia was treated using a computerized algorithm targeting for glucose levels of 4.0-7.0 mmol/l. Five thousand eight hundred twenty-eight patients were eligible for analyses, of whom 1,339 patients had a medical and 4,489 had a surgical admission diagnosis. RESULTS: The cohorts were subdivided in quintiles of increasing mean glucose. We examined the relation between these mean glucose strata and mortality. In both cohorts we observed the highest mortality in the lowest and highest strata. Logistic regression analysis adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, admission duration and occurrence of severe hypoglycemia showed that in the medical cohort mean glucose levels <6.7 mmol/l and >8.4 mmol/l and in the surgical cohort mean glucose levels < 7.0 mmol/l and >9.4 mmol/l were associated with significantly increased ICU mortality (OR 2.4-3.0 and 4.9-6.2, respectively). Limitations of the study were its retrospective design and possible incomplete correction for severity of disease. CONCLUSIONS: Mean overall glucose during ICU admission is related to mortality by a U-shaped curve in medical and surgical patients. In this cohort of patients a 'safe range' of mean glucose regulation might be defined approximately between 7.0 and 9.0 mmol/l.