Faculty Bibliography

PURPOSE/OBJECTIVE:To compare the effectiveness of continuous infusion of hydrocortisone versus intermittent boluses in the resolution of septic shock. METHODS:A retrospective chart review was performed to investigate the effects of low-dose hydrocortisone continuous infusion (200 mg per day) versus intermittent boluses (50 mg every six hours) in septic shock patients who did not respond to fluid resuscitation and vasopressors. The primary outcome was time to resolution of shock, defined by time from the initiation of hydrocortisone to time of vasopressor withdrawal when mean arterial pressure was greater than 65 mm Hg. Hospital length of stay, intensive care unit (ICU) length of stay, 28-day all-cause in-hospital mortality, and hyperglycemia were secondary outcomes. RESULTS:= 0.04). CONCLUSION/CONCLUSIONS:There was no significant difference in time to resolution of septic shock between continuous infusion (200 mg per day) and intermittent boluses (50 mg every six hours) of hydrocortisone. There were also no statistically significant differences in overall hospital length of stay, ICU length of stay, and 28-day all-cause in-hospital mortality. However, there was a significant difference in the incidence of hyperglycemia between the two groups, with patients in the bolus group experiencing more hyperglycemia than those in the continuous infusion group.

PURPOSE:The goal of this pharmacokinetic (PK) study was to evaluate whether a single 2-g prophylactic dose of cefazolin given (IV) bolus provides effective protective cefazolin levels for prophylaxis against methicillin-sensitive S. aureus (MSSA), the primary skin pathogen in bariatric surgery. MATERIALS AND METHODS:Thirty-seven patients having gastric bypass or sleeve gastrectomy received cefazolin 2-g preoperative prophylaxis. Serum, subcutaneous adipose tissue, and deep peri-gastric adipose tissue specimens were collected at incision and before skin closure. Cefazolin concentrations in serum and adipose tissue were determined by high-performance liquid chromatography. RESULTS:Penetration of cefazolin, a water soluble antibiotic, into adipose tissue was only 6-8 % of simultaneous serum levels. However, cefazolin tissue concentrations in all adipose tissue specimens, exceeded mean MIC for MSSA. CONCLUSIONS:not dose-dependent. Extremely high-dosed cefazolin, i.e., 3 or 4 g is excessive and unnecessary for bariatric surgery prophylaxis. A single cefazolin 2 g preoperative dose also eliminates the need for intraoperative redosing at 4 h.

BACKGROUND:Glucagon-like peptide-1 (GLP-1) level was significantly increased post Vertical Sleeve Gastrectomy (VSG), an effect believed to contribute to its beneficial cardiometabolic effects. OBJECTIVE:To validate the beneficial GLP-1 mediated cardiometabolic effects post VSG using GLP-1 antagonist (exendin 9-39) in Zucker diabetic fatty rats. METHODS:Animals were divided into three (n = 5) groups: (i) sham, (ii) VSG, and (iii) VSG received exendin 9-39 (GLP-1 receptor antagonist). The study was performed over 12 weeks and parameters were measured 12 weeks post-surgery. RESULTS AND DISCUSSION/CONCLUSIONS:As expected, fasting blood glucose and insulin levels were improved post VSG due to enhanced GLP-1 secretion. However, both fasting glucose and insulin levels were impaired in the presence of GLP-1 antagonist. Baseline total cholesterol level pre-surgery was 100±1 mg/dl which remained unchanged in the VSG group but significantly increased to 140±8 mg/dl in the presence of antagonist. Interestingly, post-surgery there was a nearly 70% reduction in triglyceride level in the VSG group compared to sham which was overcome in the presence of antagonist. Myographic studies using aortic rings showed no significant change between groups. Additionally, blood pressure and heart rate also remained unchanged in all groups. Serum bile acid and L-PGDS levels increased post VSG but significantly decreased in the presence of antagonist, suggesting a strong association with GLP-1 and a novel mechanism of action. CONCLUSION/CONCLUSIONS:Enhanced GLP-1 secretion post VSG imparted beneficial cardiometabolic effects on blood glucose, insulin, total cholesterol, triglyceride, bile acids and L-PGDS levels which were abated in the presence of GLP-1 antagonist.

BACKGROUND:Vertical sleeve gastrectomy (VSG) ameliorates metabolic complications in obese and diabetic patients through unknown mechanisms. OBJECTIVE:synthase (L-PGDS) in glucose regulation in response to VSG using L-PGDS knock-out (KO), knock-in (KI), and C57BL/6 (wild type) mice. SETTING/METHODS:Winthrop University Hospital Research Institute. METHODS:Animals were divided into 6 groups: L-PGDS KO sham/VSG (n = 5), L-PGDS KI sham/VSG (n = 5), and C57BL/6 (wild type) sham/VSG (n = 5). Related parameters were measured in fasting animals after 10 weeks. RESULTS:Our intraperitoneal glucose tolerance tests and homeostatic model assessment insulin resistance results showed significant glycemic improvement 10 weeks post-VSG in both C57BL/6 and KI groups compared with the sham group. In contrast, the KO group developed glucose intolerance and insulin resistance similar to or greater than the sham group 10 weeks post-VSG. Interestingly, weight gain was insignificant 10 weeks post-VSG in all the groups and even trended higher in the KO group compared with sham. Peptide YY levels in the KO group post-VSG were slightly increased but significantly less than other groups. Similarly, the KO group showed significantly less leptin sensitivity in response to VSG compared with the KI group. Total cholesterol level remained unchanged in all groups irrespective of sham or surgery but interestingly, the KO group had significantly higher cholesterol levels. In parallel, adipocyte size was also found to be significantly increased in the KO group post-VSG compared with the sham group. CONCLUSION/CONCLUSIONS:Our findings propose that L-PGDS plays an important role in the beneficial metabolic effects observed after VSG.

OBJECTIVE:To assess the prevalence of delirium and coma in mechanically ventilated patients sedated with dexmedetomidine or propofol alone; to evaluate the hospital length of stay for both treatment groups; and to evaluate the level of sedation, adverse effects, and hospital outcomes. METHODS:Medical records were reviewed retrospectively for patients who were admitted to the medical or surgical intensive care units (ICUs) in a 591-bed teaching hospital and who received either dexmedetomidine or propofol alone for 24 hours or more for sedation. RESULTS:A total of 111 patients were included in the study, with 56 patients in the dexmedetomidine group and 55 patients in the propofol group. Results of the analysis showed that the propofol group had a higher prevalence of coma (43.6% versus 12.5%; P < 0.001). Dexmedetomidine patients had a longer median hospital length of stay of 23.5 days (interquartile range [IQR], 11.5-39.5 days) versus 15.0 days (IQR, 7.0-24.0 days; P = 0.01). The rates of delirium were similar in both groups, with 16% in dexmedetomidine-treated patients versus 20% in propofol-treated patients (P = 0.63). CONCLUSION/CONCLUSIONS:No difference in the prevalence of delirium was found when comparing the dexmedetomidine- and propofol-treated groups. Propofol was associated with more coma and oversedation; dexmedetomidine was associated with longer time to extubation, longer length of stay in the ICU, and longer hospital length of stay.