Leonid Koyfman

Inhibition of Cyclooxygenase 2 by Nimesulide Decreases Prostaglandin E2 Formation But Does Not Alter Brain Edema or Clinical Recovery After Closed Head Injury in Rats

Recently, the enzyme cyclooxygenase (COX) has been recognized to exist as constitutive (COX-1) and inducible isoforms (COX-2). In previous studies, drugs that were inhibitors of both COX-1 and COX-2 failed to decrease brain edema formation or improve Neurological Severity Score (NSS) after closed head trauma (CHT), although some did decrease prostaglandin-E2 (PGE2) formation. The present study examined whether or not a specific inhibitor of COX-2 (nimesulide) exerts a beneficial effect after CHT in rats. Halothane-anesthetized rats (n = 8 in each group) were randomly assigned to one of four groups: surgery, no CHT, no drug (group 1); surgery, no CHT, nimesulide 30 mg/kg intraperitoneally (IP) (group 2); surgery, CHT, no drug (group 3); and surgery, CHT, nimesulide 30 mg/kg IP (group 4). NSS was determined at 1 and 24 h, and brain tissue PGE2 concentration and water content were determined after killing at 24 h. Treatment with nimesulide did not improve NSS (NSS at 24 h = 11+/-6 [median +/- range] in group 3 and 12+/-4 in group 4) or edema formation (brain water content at 24 h = 84.3+/-1.8% [mean +/- SD] in group 3 and 83.8+/-1.9% in group 4). However, nimesulide did decrease cortical and hypothalamic PGE2 formation by 41% and 47%, respectively during the first hour of incubation after brain tissue sampling. The authors conclude that although nimesulide does reduce tissue PGE2 formation, it does not exert a beneficial effect on brain tissue edema or functional activity after CHT in rats.

Phenylephrine-induced hypertension does not improve outcome after closed head trauma in rats.

Phenylephrine-induced hypertension (increase of 30-35 mm Hg for 15 min) is reported to increase cerebral perfusion pressure and collateral flow to ischemic areas of the brain in a rat model of focal cerebral ischemia. In the present study, we examined whether phenylephrine-induced hypertension of similar magnitude and duration was beneficial in a rat model of closed head trauma (CHT). Forty-eight rats were randomized into four experimental conditions: CHT at time 0 min (yes/no), plus phenylephrine-induced hypertension (increase of 30-35 mm Hg for 15 min) at 65 min (yes/no). CHT was delivered using a weight-drop device (0.5 J). Outcome measures were neurological severity score (NSS) at 1, 4, and 24 h, and brain tissue specific gravity (microgravimetry) and injury volume (2,3,5-triphenyltetrazoium chloride) at 24 h. After CHT, NSS at 24 h (median +/- range) and brain tissue specific gravity (mean +/- SD, injured hemisphere) were 7 +/- 2 and 1.033 +/- 0.007 without phenylephrine and 8 +/- 2 and 1.035 +/- 0.005 with phenylephrine (P = 0.43), respectively. Tissue injury volume (mean +/- SD) was 335 +/- 92 mm3 without phenylephrine and 357 +/- 154 mm3 with phenylephrine (P > 0.62). The results of our study indicate that postinjury treatment with 15 min of phenylephrine-induced hypertension does not attenuate brain edema, reduce tissue injury volume, or improve neurological outcome after CHT in rats. Implications: Phenylephrine-induced hypertension is reported to increase cerebral perfusion pressure and blood flow in a rat model of focal cerebral ischemia. In our study, phenylephrine-induced hypertension did not decrease brain edema or tissue injury volume or improve neurological outcome in a rat model of closed head trauma. (Anesth Analg 1998;87:574-8)

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.

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.

Severe traumatic brain injury and controlled hemorrhage in rats: quest for the optimal mean arterial blood pressure after whole fresh donor blood resuscitation.

ABSTRACT Treatment of combined traumatic brain injury and hypovolemic shock poses a particular challenge due to the possible conflicting consequences. While restoring diminished volume is the treatment goal for hypovolemia, maintaining and adequate cerebral perfusion pressure and avoidance of secondary damage remain a treatment goal for the injured brain. Various treatment modalities have been proposed, but the optimal resuscitation fluid and goals have not yet been clearly defined. In this study, we investigate the physiological and neurological outcomes in a rat model of combined traumatic brain injury and hypovolemic shock, submitted to treatment with varying amounts of fresh blood. Forty-eight male Lewis rats were divided into control and treatment groups. Traumatic brain injury was inflicted by a free-falling rod on the exposed cranium. Hypovolemia was induced by controlled hemorrhage of 30% blood volume. Treatment groups were treated by fresh whole blood with varying volumes, reaching resuscitation goals of a mean arterial blood pressure (MAP) of 80, 100, and 120 mmHg at 15 min. Mean arterial blood pressure was assessed at 60 min and neurological outcomes and mortality in the subsequent 48 h. At 60 min, MAP was highest for the group resuscitated most aggressively. Neurological outcomes and mortality inversely correlated with the aggressiveness of resuscitation. In this study, we find that mild resuscitation with goals of restoring MAP to 80 mmHg (which is lower than baseline) provided best results when considering hemodynamic stability, survival, and neurological outcomes. An aggressive resuscitation may be detrimental, inducing processes that eventually cause a significant decrease in survival.

Multidrug Resistance Acinetobacter Bacteremia Secondary to Ventilator-Associated Pneumonia: Risk Factors and Outcome

Purpose: Acinetobacter baumannii is a multidrug resistant (MDR), gram-negative bacterium commonly implicated in ventilator-associated pneumonia (VAP) in critically ill patients. Patients in the intensive care unit (ICU) with VAP often subsequently develop A baumannii bacteremia, which may significantly worsen outcomes. Materials and Methods: In this study, we retrospectively reviewed the clinical and laboratory records of 129 ICU patients spanning 6 years with MDR A baumannii VAP; 46 (35%) of these patients had concomitant MDR A baumannii bacteremia. Results: The ICU mortality rate was higher in patients with VAP having A baumannii bacteremia compared to nonbacteremic patients (32.4% vs 9.6% respectively, P < .005). Age >65 years, an Acute Physiology and Chronic Health Evaluation II (APACHE-II) score higher than 20, a Sequential Organ Failure Assessment (SOFA) score higher than 7 on the day of bacteremia, and the presence of comorbid disease (chronic obstructive pulmonary disease [COPD] and chronic renal failure) were found to be independent risk factors for in-hospital mortality in this population. Multidrug resistant A baumannii was not an independent risk factor for mortality. Conclusion: Although the presence of comorbid diseases (COPD and chronic renal failure) and severity of disease (APACHE > 20 and SOFA >7) were found to be independent risk factors for ICU mortality, MDR A baumannii bacteremia was not an independent risk factor for mortality in our critically ill population.

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.

Cardiac Arrhythmias in a Septic ICU Population: A Review

Abstract Progressive cardiovascular deterioration plays a central role in the pathogenesis of multiple organ failure (MOF) caused by sepsis. Evidence of various cardiac arrhythmias in septic patients has been reported in many published studies. In the critically ill septic patients, compared to non-septic patients, new onset atrial fibrillation episodes are associated with high mortality rates and poor outcomes, amongst others being new episodes of stroke, heart failure and long vasopressor usage. The potential mechanisms of the development of new cardiac arrhythmias in sepsis are complex and poorly understood. Cardiac arrhythmias in critically ill septic patients are most likely to be an indicator of the severity of pre-existing critical illness.

Traumatic Page Kidney Induced Hypertension in Critical Care: Immediately Resolved or Long-Term Resistant Problem

Page kidney is a well-known phenomenon causing hypertension, due to compression of renal parenchyma by a subcapsular hematoma, of either traumatic or non-traumatic origin. The main therapeutic approach is based on surgical approach (nephrectomy or hematoma evacuation) and antihypertensive treatment. In this paper we present a post-traumatic case of Page Kidney in a Critical Care unit. We discuss different therapeutical opportunities to extremely elevated systemic blood pressure resistant to traditional drug therapy.

Inguinal Herniation of the Urinary Bladder Presenting as Recurrent Urinary Retention

Herniation of the urinary bladder into the inguinal canal is an uncommon finding, observed in 0.5–4% of inguinal hernias (Curry (2000)). It is usually associated with other conditions that increase intra-abdominal pressure such as bladder neck obstruction due to prostatic hypertrophy. Consequently, in men, it is usually associated with some degree of urinary retention. We present a 42-year-old man in whom herniation of the urinary bladder was the cause of urinary retention, and not vice versa. The patient was on tumor necrosis factor alpha antagonist (TNFA) (Etanercept) for severe Ankylosing spondylitis. Initially, the urinary retention was thought to be a side effect of the medication, but after the drug was discontinued, urinary retention persisted. CT and MRI demonstrated huge herniation of the urinary bladder into the inguinal canal. Immediately after the hernia was repaired, bladder function was restored. TNF treatment was restarted, and no further urinary symptoms were observed in the next two years of follow-up. In this case, the primary illness and its treatment were distracting barriers to early diagnosis and treatment. In younger patients with a large hernia who develop unexpected urinary retention, herniation of the urinary bladder should be highly considered in the differential diagnosis.