1410: IMPACT OF NOREPINEPHRINE DOSING STRATEGY IN ACHIEVING GOAL MAP IN OBESE PATIENTS WITH SEPTIC SHOCK

Background: Currently, a lack of standardization exists in norepinephrine dosing units, the first-line vasopressor for septic shock. Timely achievement of goal mean arterial pressure (MAP) is dependent on optimal vasopressor dosing. Objective: To determine if weight-based dosing (WBD) of norepinephrine leads to earlier time to goal MAP compared with non-WBD in obese patients with septic shock. Methods: This was a retrospective, multicenter cohort study. Patients had a body mass index (BMI) ≥30 kg/m2 and received norepinephrine for septic shock with either a non-WBD strategy (between December 2009 and January 2013) or WBD strategy (between January 2013 and December 2015). The primary outcome was time to goal MAP. Secondary outcomes were norepinephrine duration, dose requirements, and development of treatment-related complications. Results: A total of 287 patients were included (WBD 144; non-WBD 143). There was no difference in median time to goal MAP (WBD 58 minutes, interquartile range [IQR] = 16.8-118.5, vs non-WBD 60 minutes, IQR = 17.5-193.5; P = 0.28). However, there was a difference in median cumulative norepinephrine dose (WBD 12.6 mg, IQR = 4.9-45.9, vs non-WBD 10.5 mg, IQR = 3.9-25.6; P = 0.04) and time to norepinephrine discontinuation (WBD 33 hours, IQR = 15-69, vs non-WBD 27 hours, IQR = 12-51; P = 0.03). There was no difference in rates of atrial fibrillation (WBD 15.3% vs non-WBD 23.7%; P = 0.07) or mortality (WBD 23.6% vs non-WBD 23.1%; P = 0.92). Conclusion: WBD of norepinephrine does not achieve time to goal MAP earlier in obese patients with septic shock. However, WBD may lead to higher norepinephrine cumulative dose requirements and prolonged time until norepinephrine discontinuation.

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Effect of Vasopressin Dose on Hemodynamic Response in Obese Patients With Septic Shock: A Retrospective Observational Study

Annals of Pharmacotherapy ◽

10.1177/10600280211007213 ◽

2021 ◽

pp. 106002802110072

Author(s):

Casey A. Dubrawka ◽

Kevin D. Betthauser ◽

Hannah E. Pope ◽

Gabrielle A. Gibson

Keyword(s):

Septic Shock ◽

Retrospective Cohort ◽

Primary Outcome ◽

Standard Dose ◽

Hemodynamic Response ◽

Percentage Change ◽

High Dose ◽

Obese Patients ◽

Improved Outcomes ◽

Higher Doses

Background No clear association between standard vasopressin doses and body mass index exists, despite potential pharmacokinetic and pharmacodynamic variability among patients with septic shock. It is unknown if higher doses may alter hemodynamic response. Objective The purpose of this study was to evaluate the effect of vasopressin dose on hemodynamic response in obese patients with septic shock. Methods A single-center, retrospective cohort study was conducted in adult, obese patients with septic shock receiving catecholamine vasopressors and vasopressin. Patients were analyzed according to vasopressin dose received: standard dose (≤0.04 U/min) and high dose (>0.04 U/min). The primary outcome was percentage change in norepinephrine equivalent (NEQ) dose. Results A total of 182 patients were included in the analysis, with 136 in the standard-dose vasopressin group and 46 in the high-dose vasopressin group. There was no difference in percentage change in NEQ dose at 6 hours after standard- or high-dose vasopressin attainment (−28.6% vs −19.1%; P = 0.166). A greater increase in mean arterial pressure (MAP) at 6 hours was observed with receipt of high-dose vasopressin (23.3% vs 15.3%; P = 0.023). Duration of shock and length of stay were significantly longer in patients who received high-dose vasopressin, with no difference in in-hospital mortality. Conclusion and Relevance This represents the first analysis comparing standard and higher doses of vasopressin in obese patients with septic shock. Receipt of high-dose vasopressin was not associated with a difference in catecholamine requirement or improved outcomes. Further studies are warranted to provide guidance on the use of high-dose vasopressin in septic shock.

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Norepinephrine Dosing in Obese and Nonobese Patients With Septic Shock

American Journal of Critical Care ◽

10.4037/ajcc2016667 ◽

2016 ◽

Vol 25 (1) ◽

pp. 27-32 ◽

Cited By ~ 10

Author(s):

John J. Radosevich ◽

Asad E. Patanwala ◽

Brian L. Erstad

Keyword(s):

Body Mass Index ◽

Septic Shock ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Body Mass ◽

Secondary Outcome ◽

Obese Patients ◽

Hemodynamic Status ◽

Norepinephrine Infusion ◽

Nonobese Patients

Background Whether or not norepinephrine infusions for support of hemodynamic status in patients with septic shock should be weight based is unknown. This situation is particularly pertinent in patients who are extremely overweight or obese. Objective To compare dosing requirements and effect of norepinephrine on blood pressure in obese and nonobese patients with septic shock. Methods In a retrospective cohort study, data on adult patients with septic shock who received norepinephrine infusion for support of hemodynamic status in a tertiary care, academic medical center were analyzed. Patients were categorized as obese (body mass index ≥ 30) or nonobese (body mass index < 30). The primary outcome was dosing requirements of norepinephrine at 60 minutes after the start of the infusion. The secondary outcome was the log-transformed ratio of mean arterial pressure to norepinephrine. Results The final cohort consisted of 100 obese and 100 nonobese patients. Mean norepinephrine infusion rate at 60 minutes was 0.09 (SD, 0.08) μg/kg per minute in the obese group and 0.13 (SD, 0.14) μg/kg per minute in the nonobese group (P = .006). The non–weight-based dose at 60 minutes was 9 μg/min in obese patients and 8 μg/min in nonobese patients (P = .72). The log transformed mean arterial pressure to norepinephrine ratio at 60 minutes was 2.5 (SD, 0.9) in obese patients and 2.5 (SD, 0.8) in nonobese patients (P = .54) Conclusions Compared with nonobese patients, obese patients with septic shock require lower weight-based doses of norepinephrine and similar total norepinephrine doses.

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Favorable 90-Day Mortality in Obese Caucasian Patients with Septic Shock According to the Sepsis-3 Definition

Journal of Clinical Medicine ◽

10.3390/jcm9010046 ◽

2019 ◽

Vol 9 (1) ◽

pp. 46 ◽

Cited By ~ 1

Author(s):

Caspar Mewes ◽

Carolin Böhnke ◽

Tessa Alexander ◽

Benedikt Büttner ◽

José Hinz ◽

...

Keyword(s):

Septic Shock ◽

Protective Effect ◽

Cox Regression ◽

Obese Patients ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Threatening Condition ◽

Life Threatening ◽

Caucasian Patients ◽

Patient Prognosis

Septic shock is a frequent life-threatening condition and a leading cause of mortality in intensive care units (ICUs). Previous investigations have reported a potentially protective effect of obesity in septic shock patients. However, prior results have been inconsistent, focused on short-term in-hospital mortality and inadequately adjusted for confounders, and they have rarely applied the currently valid Sepsis-3 definition criteria for septic shock. This investigation examined the effect of obesity on 90-day mortality in patients with septic shock selected from a prospectively enrolled cohort of septic patients. A total of 352 patients who met the Sepsis-3 criteria for septic shock were enrolled in this study. Body-mass index (BMI) was used to divide the cohort into 24% obese (BMI ≥ 30 kg/m2) and 76% non-obese (BMI < 30 kg/m2) patients. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality (31% vs. 43%; p = 0.0436) in obese patients compared to non-obese patients. Additional analyses of baseline characteristics, disease severity, and microbiological findings outlined further statistically significant differences among the groups. Multivariate Cox regression analysis estimated a significant protective effect of obesity on 90-day mortality after adjustment for confounders. An understanding of the underlying physiologic mechanisms may improve therapeutic strategies and patient prognosis.

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Vancomycin Pharmacokinetics in Obese Patients with Sepsis or Septic Shock

Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy ◽

10.1002/phar.2367 ◽

2020 ◽

Vol 40 (3) ◽

pp. 211-220

Author(s):

Anne M. Masich ◽

Shamir N. Kalaria ◽

Jeffrey P. Gonzales ◽

Emily L. Heil ◽

Asha L. Tata ◽

...

Keyword(s):

Septic Shock ◽

Obese Patients

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1029. Clinical and economic outcomes of a newly implemented daptomycin dosing policy in a four-hospital health system

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.893 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S362-S362

Author(s):

Meredith Todd ◽

Kelci Jones ◽

Sharon Hill

Keyword(s):

Antimicrobial Stewardship ◽

Medical Center ◽

Pharmacokinetic Data ◽

Antimicrobial Stewardship Program ◽

Obese Patients ◽

Pharmacy Department ◽

Stewardship Program ◽

Increased Risk ◽

Dosing Strategy ◽

Drug Waste

Abstract Background In light of recently published clinical and pharmacokinetic data regarding the use of daptomycin in obese patients, the Charleston Area Medical Center (CAMC) Antimicrobial Stewardship Program implemented an adjusted body weight dosing strategy for obese patients. Along with this new dosing strategy, an effort to reduce drug waste was also implemented by restricting the timing of routinely scheduled daptomycin doses for inpatients. This study aims to determine the clinical outcomes for patients receiving daptomycin both before and after this policy change. Secondary objectives include assessing creatinine phosphokinase (CK) levels in the study participants, defining the risk of CK elevation with the coadministration of HMG Co-A reductase inhibitors and daptomycin, and assessing any reduction in drug waste for the pharmacy department. Methods This study is a single-center, one-group pretest-posttest, quasi-experimental study evaluating the implementation of a two-part daptomycin dosing policy. The pretest group included all patients meeting inclusion and exclusion criteria that received daptomycin at CAMC from September 1 - November 30, 2017. The new daptomycin dosing policy was implemented on September 1, 2018. The posttest group included all patients meeting the stated criteria that received daptomycin from September 1 - November 30, 2018. Results A total of 118 patients were included in this study. There were 5 (7.7%) treatment failures in the pretest group and 3 (5.7%) in the posttest group (P = 0.7). Of the patients with CK levels monitored, 6 (33%) were found to have significant elevations in the pretest group and 4 (40%) were found in the posttest group (P = 0.6). There was no difference observed in the risk of CK elevation with daptomycin administration in the presence of an HMG-CoA reductase inhibitor. For the two time periods reviewed, the pharmacy department purchased fewer vials of daptomycin in the posttest group. Conclusion Patients at CAMC receiving daptomycin after implementation of a new dosing policy did not experience an increased risk of treatment failure. The Antimicrobial Stewardship Program will continue to monitor patients receiving daptomycin therapy at CAMC. Disclosures All authors: No reported disclosures.

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Therapeutic Drug Monitoring (TDM) of IV Busulfan in Patients with Severe Obesity.

Blood ◽

10.1182/blood.v110.11.1990.1990 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1990-1990

Author(s):

Donald A. Hutcherson ◽

Jolynn K. Sessions ◽

Ronald A. Mihelic ◽

Katherine Sanvidge ◽

Stephen R. Stricker ◽

...

Keyword(s):

Body Weight ◽

Severe Obesity ◽

Package Insert ◽

Ideal Body Weight ◽

Obese Patients ◽

Actual Weight ◽

Severely Obese ◽

Ideal Body ◽

The Mean ◽

Dosing Strategy

Abstract It has been previously reported that increases in relapse and graft rejection can be associated with a low busulfan area under the curve (AUC) and hepatic toxicities are associated with a high AUC. This has lead to strategies to adjust busulfan dosing to achieve a target AUC. A retrospective analysis was performed in patients with severe obesity, defined as a Body Mass Index (BMI) greater than 40, to evaluate the reliability of IV busulfan dosed using the package insert dosing strategy to reach a targeted AUC. The study included 11 females and 8 males who received IV busulfan as part of their hematopoietic progenitor cell transplant preparative regimen. There were 11 autologous and 8 allogeneic transplants for lymphoma (10) and leukemia (9). The mean and median ages were 38 and 41 years (range 19–51). The mean and median BMIs for this population were 47.8 and 46.2 (range 40.4–62.7). The mean and median weights were 139.5 kg and 142.5 kg (range 107–192.3). TDM was performed with the first dose of busulfan along with subsequent dosage adjustments to achieve a target AUC of 1150–1350 micromol X min/L. Busulfex package insert dosing recommendations are for 16 doses of 0.8 mg/kg (12.8 mg/kg) using an adjusted ideal body weight (AIBW) for obese patients. AIBW = 0.25 × (actual weight − ideal body weight) + ideal body weight. Using the AIBW dosing, the mean starting dose to actual body weight ratio was 0.48 mg/kg (range 0.40–0.55 mg/kg). Based on the AUC analysis, the predicted mean AUC using the AIBW dosing was 972 (range 702–1356). Six AUCs were below 900, 10 AUCs were above 900 but below 1150, 2 AUCs were within the target range and 1 AUC was greater than 1350. Thirteen of the patients had repeat AUC analyses following a subsequent dose to confirm that the dose adjustments achieved the targeted AUCs. Seven of these patients had further dose adjustments following the repeat AUC analysis. Five patients with a busulfan mean half-life of 235 minutes (range 218–247 minutes) had higher AUCs than the rest of the group. The mean and median AUCs for these 5 patients were 1177 and 1223 (range 997–1357). The remaining 14 patients with a mean busulfan half-life of 177 minutes (range 151–201) had mean and median AUCs of 899 and 903 (range 702–1105). The total therapy delivered ranged from 12.7 to 21.4 mg/kg based on the AIBW. When calculated on actual weight, the range was 6.9 to 11.24 mg/kg. Conclusion: The AIBW dosing strategy of IV busulfan is inadequate to achieve the targeted AUC of 1150–1350 in severely obese patients. Severely obese patients require dose increases in the majority of cases, while those with delayed clearance could be overdosed if higher doses are administered without TDM. Severely obese patients require TDM and the majority will require dosage adjustments to administer IV busulfan in the targeted therapeutic range.

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