Ruslan Kutz

Neuroprotection by Estrogen and Progesterone in Traumatic Brain Injury and Spinal Cord Injury

In recent years there has been a growing body of clinical and laboratory evidence demonstrating the neuroprotective effects of estrogen and progesterone after traumatic brain injury (TBI) and spinal cord injury (SCI). In humans, women have been shown to have a lower incidence of morbidity and mortality after TBI compared with age-matched men. Similarly, numerous laboratory studies have demonstrated that estrogen and progesterone administration is associated with a mortality reduction, improvement in neurological outcomes, and a reduction in neuronal apoptosis after TBI and SCI. Here, we review the evidence that supports hormone-related neuroprotection and discuss possible underlying mechanisms. Estrogen and progesterone-mediated neuroprotection are thought to be related to their effects on hormone receptors, signaling systems, direct antioxidant effects, effects on astrocytes and microglia, modulation of the inflammatory response, effects on cerebral blood flow and metabolism, and effects on mediating glutamate excitotoxicity. Future laboratory research is needed to better determine the mechanisms underlying the hormones’ neuroprotective effects, which will allow for more clinical studies. Furthermore, large randomized clinical control trials are needed to better assess their role in human neurodegenerative conditions.

Positive fluid balance as a major predictor of clinical outcome of patients with sepsis/septic shock after ICU discharge

INTRODUCTION Sepsis and septic shock continue to be syndromes that carry a high mortality rate worldwide. Early aggressive fluid and vasopressor support have resulted in significant improvement in patient outcomes. The prognostic clinical significance of a positive fluid balance in septic intensive care unit (ICU) patients remains undetermined. METHODS We collected data from 297 septic patients hospitalized in our general and medical ICUs at Soroka Medical Center between January 2005 and June 2011 and divided the 4 study groups into the following 4 fluid balances: group 1, patients with fluid balance at discharge from ICU (FBD) less than 10 L; group 2, patients with an FBD of 10 to 20 L; group 3, patients with an FBD of 20 to 30 L; and group 4, patients with FBD in excess of 30 L. RESULTS The ICU and in-hospital mortality rate was also significantly higher in groups 2 to 4 as compared with group 1 (P < .001 for both ICU and in-hospital mortality). The positive cumulative FBD was found to be an independent predictor of ICU mortality (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06; P < .001; Table 3) and in-hospital mortality (OR, 1.06; 95% CI, 1.03-1.08; P < .001; Table 5) and also to constitute a risk factor for new organ system dysfunction at hospital discharge (OR, 1.01; 95% CI, 1.01-1.013; P < .001; Table 6) in critically ill patients with severe sepsis/septic shock. CONCLUSIONS Although it is a monocentric retrospective study, we suggest that positive cumulative fluid balance is one of the major factors that can predict the clinical outcome of critically ill patients during their ICU stay and after their discharge from the ICU.

Establishment of an animal model of depression contagion.

BACKGROUND Depression is a common and important cause of morbidity, and results in a significant economic burden. Recent human studies have demonstrated that that depression is contagious, and depression in family and friends might cumulatively increase the likelihood that a person will exhibit depressive behaviors. The mechanisms underlying contagion depression are poorly understood, and there are currently no animal models for this condition. METHODS Rats were divided into 3 groups: depression group, contagion group, and control group. After induction of depression by 5 weeks of chronic unpredictable stress, rats from the contagion group were housed with the depressed rats (1 naïve rat with 2 depressed rats) for 5 weeks. Rats were then subjected to sucrose preference, open field, and forced swim tests. RESULTS The sucrose preference was significantly reduced in the depressed rats (p<0.01) and contagion depression rats (p<0.01). Climbing time during forced swim test was reduced in the depression and contagion depression groups (p<0.001), whereas immobility time was significantly prolonged in only the depression group (p<0.001). Rats in both the depression (p<0.05) and depression contagion group (p<0.005) had decreased total travel distance and decreased mean velocity in the open field test, whereas the time spent in the central part was significantly shorter in only the depression group (p<0.001). CONCLUSIONS In this study, for the first time we demonstrated depression contagion in an animal model. A reliable animal model may help better understand the underlying mechanisms of contagion depression, and may allow for future investigations of the studying therapeutic modalities.

Association between Hypophosphatemia and Cardiac Arrhythmias in the Early Stage of Sepsis: Could Phosphorus Replacement Treatment Reduce the Incidence of Arrhythmias?

It is well known that new-onset arrhythmias are common in septic patients. It is thought that hypophosphatemia in the early stages of sepsis may contribute to the development of new arrhythmias. In this study, we hypothesized that intravenous (IV) phosphorus replacement may reduce the incidence of arrhythmias in critically ill patients. 34 adult septic patients with hypophosphatemia admitted to the general intensive care unit were treated with IV phosphorus replacement per ICU protocol, and the incidence of new arrhythmias were compared with 16 patients from previously published data. IV phosphorus replacement was associated with a significantly reduced incidence of arrhythmias (38% vs. 63%, p=0.04). There were no differences in observed mortality between subgroups, which may be due to the small sample size. This study demonstrated that IV phosphorus replacement might be effective in reducing the incidence of new arrhythmias in septic patients.

Anesthetic Management of Patients with Congenital Insensitivity to Pain with Anhidrosis: A Retrospective Analysis of 358 Procedures Performed Under General Anesthesia.

BACKGROUND:Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder characterized by recurrent episodic fevers, anhidrosis, absent reaction to noxious stimuli, self-mutilating behavior, and mental retardation. The anesthetic management of patients with CIPA is challenging. Autonomic nervous system abnormalities are common, and patients are at increased risk for perioperative complications. METHODS:In this study, we describe our experience with 35 patients with CIPA who underwent 358 procedures requiring general anesthesia between 1990 and 2013. RESULTS:During surgery, 3 patients developed hyperthermia intraoperatively (>37.5°C) without prior fever. There were no cases of intraoperative hyperpyrexia (>40°C). Aspiration was suspected in 2 patients, and in another patient aspiration was prevented by the use of endotracheal tube, early detection of regurgitation, and aggressive suctioning. One patient had cardiac arrest requiring cardiopulmonary resuscitation. Intraoperative bradycardia was observed in 10 cases, and postoperative bradycardia was observed in 11 cases. CONCLUSIONS:Regurgitation, hyperthermia, and aspiration were uncommon, but the incidence of bradycardia was higher than has been reported in previous studies. CIPA remains a challenge for anesthesiologists. Because of the rare nature of this disorder, the risk of various complications is difficult to predict.

Epidemiology of new-onset paroxysmal atrial fibrillation in the General Intensive Care Unit population and after discharge from ICU. A retrospective epidemiological study

BACKGROUND Evidence of various cardiac arrhythmias in septic patients has been demonstrated by multiple clinical reports and observations. Most cardiac arrhythmias in sepsis are new-onset and may be related to sepsis-induced myocardial dysfunction. We propose to investigate and analyze data of new-onset paroxysmal atrial fibrillation (AF) in a critically ill septic population. METHODS This is a retrospective epidemiologic study. We collected clinical data from two hundred septic patients who developed a new episode of atrial fibrillation during their hospitalization in General Intensive Care Unit (GICU) between January 2007 and June 2013. RESULTS Of these 200 septic patients, 81 septic patients developed a new episode of AF and included in the present study. Thirty-seven patients had no past medical history of atrial fibrillation (AF) or antiarrhythmic therapy (new episode of atrial fibrillation, Group 1) and 44 had previously known episodes of atrial fibrillation and were prescribed antiarrhythmic therapy at home (Group 2). Group 2 patients had longer duration of recurrent episodes of atrial fibrillation compared to patients in Group 1 (11.07 ± 8.7 vs. 7.4 ± 6.1 days; P = 0.013). The overall ICU and in-hospital mortality rate was similar in both study groups. There was no significant difference in new stroke and pulmonary embolism (PE) between both study groups (P > 0.05). CONCLUSION In the present study we demonstrated no difference in morbidity and mortality rate in-ICU and after discharge between septic patients who had previous AF episodes and patients who had no previous past medical history of any cardiac arrhythmias.

Use of early inhaled nitric oxide therapy in fat embolism syndrome to prevent right heart failure.

Fat embolism syndrome (FES) is a life-threatening condition in which multiorgan dysfunction manifests 48–72 hours after long bone or pelvis fractures. Right ventricular (RV) failure, especially in the setting of pulmonary hypertension, is a frequent feature of FES. We report our experience treating 2 young, previously healthy trauma patients who developed severe hypoxemia in the setting of FES. Neither patient had evidence of RV dysfunction on echocardiogram. The patients were treated with inhaled nitric oxide (NO), and their oxygenation significantly improved over the subsequent few days. Neither patient developed any cardiovascular compromise. Patients with FES that have severe hypoxemia and evidence of adult respiratory distress syndrome (ARDS) are likely at risk for developing RV failure. We recommend that these patients with FES and severe refractory hypoxemia should be treated with inhaled NO therapy prior to the onset of RV dysfunction.