Cost-effectiveness of amiodarone for prophylaxis of atrial fibrillation after cardiothoracic surgery

STUDY OBJECTIVE: To determine whether prophylactic amiodarone, dosed according to Atrial Fibrillation Suppression Trial (AFIST) I and II regimens, is a cost-effective strategy for prevention of postoperative atrial fibrillation. DESIGN: Cost-effectiveness analysis of retrospective cohort study. SETTING: Urban, academic hospital. PATIENTS: A total of 2046 patients who underwent cardiothoracic surgery between February 1, 1998, and October 31, 2003. Of these patients, 186 received amiodarone and 1860 served as controls. MEASUREMENTS AND MAIN RESULTS: Each patient who received prophylactic amiodarone using the AFIST I or II dosing strategies was matched for age, sex, history of valvular surgery, history of atrial fibrillation, beta-blocker intolerance, and receipt of preoperative digoxin therapy with 10 patients who did not receive prophylactic amiodarone. Occurrence of postoperative atrial fibrillation, total hospital costs, and both intensive care unit (ICU) and total hospital length of stay (LOS) were compared between groups. Nonparametric bootstrapping was conducted to examine study results as part of a quadrant analysis and to calculate confidence intervals for the incremental cost-effectiveness ratio. The ICU and total hospital LOS, and total costs for patients with and without postoperative atrial fibrillation were also compared. Fewer patients receiving prophylactic amiodarone developed postoperative atrial fibrillation compared with controls (23.1% vs 29.9%, p=0.05). Total hospital costs for the amiodarone group were 28% less than those for the control group (24,131 US dollars +/- 26,539 vs 33,518 US dollars +/- 40,892, p=0.002). Approximately 98% of the time, patients receiving amiodarone prophylaxis fell into the quadrant that showed superior efficacy and lower total costs. Patients who developed postoperative atrial fibrillation, compared with those who did not, regardless of amiodarone prophylaxis, had a longer mean +/- SD stay in the ICU (6.9 +/- 17.1 vs 3.7 +/- 7.9 days, p<0.001), a longer mean total hospital LOS (14.8 +/- 18.8 vs 10.2 +/- 10.4 days, p+/-0.001), and higher mean total hospital costs (41,574 US dollars +/- 54,721 vs 28,968 US dollars +/- 31,046, p<0.001). CONCLUSION: Prophylactic amiodarone was shown to reduce the occurrence of postoperative atrial fibrillation as well as total hospital costs in patients undergoing cardiothoracic surgery. In patients who developed postoperative atrial fibrillation, both ICU and total hospital LOS as well as total hospital costs were increased.     

A multicentre, prospective study to evaluate costs of septic patients in Brazilian intensive care units

BACKGROUND: Sepsis has a high prevalence within intensive care units, with elevated rates of morbidity and mortality, and high costs. Data on sepsis costs are scarce in the literature, and in developing countries such as Brazil these data are largely unavailable. OBJECTIVES: To assess the standard direct costs of sepsis management in Brazilian intensive care units (ICUs) and to disclose factors that could affect those costs. METHODS: This multicentre observational cohort study was conducted in adult septic patients admitted to 21 mixed ICUs of private and public hospitals in Brazil from 1 October 2003 to 30 March 2004. Complete data for all patients admitted to the ICUs were obtained until their discharge or death. We collected only direct healthcare-related costs, defined as all costs related to the ICU stay.Enrolled patients were assessed daily in terms of cost-related expenditures such as hospital fees, operating room fees, gas therapy, physiotherapy, blood components transfusion, medications, renal replacement therapy, laboratory analysis and imaging. Standard unit costs (year 2006 values) were based on the Brazilian Medical Association (AMB) price index for medical procedures and the BRASINDICE price index for medications, solutions and hospital consumables. Medical resource utilization was also assessed daily using the Therapeutic Intervention Scoring System (TISS-28). Indirect costs were not included. RESULTS: With a mean (standard deviation [SD]) age of 61.1 +/- 19.2 years, 524 septic patients from 21 centres were included in this study. The overall hospital mortality rate was 43.8%, the mean Acute Physiology And Chronic Health Evaluation II (APACHE II) score was 22.3 +/- 5.4, and the mean Sequential Organ Failure Assessment (SOFA) score at ICU admission was 7.5 +/- 3.9.The median total cost of sepsis was $US 9632 (interquartile range [IQR] 4583-18 387; 95% CI 8657, 10 672) per patient, while the median daily ICU cost per patient was $US 934 (IQR 735-1170; 95% CI 897, 963). The median daily ICU cost per patient was significantly higher in non-survivors than in survivors, i.e. $US 1094 (IQR 888-1341; 95% CI 1058, 1157) and $US 826 (IQR 668-982; 95% CI 786, 854), respectively (p < 0.001). For patients admitted to public and private hospitals, we found a median SOFA score at ICU admission of 7.5 and 7.1, respectively (p = 0.02), and the mortality rate was 49.1% and 36.7%, respectively (p = 0.006). Patients admitted to public and private hospitals had a similar length of stay of 10 (IQR 5-19) days versus 9 (IQR 4-16) days (p = 0.091), and the median total direct costs for public ($US 9773; IQR 4643-19 221; 95% CI 8503, 10 818) versus private ($US 9490; IQR 4305-17 034; 95% CI 7610, 11 292) hospitals did not differ significantly (p = 0.37). CONCLUSIONS: The present study provides the first economic analysis of direct costs of sepsis in Brazilian ICUs and reveals that the cost of sepsis treatment is high. Despite similar ICU management, there was a significant difference regarding patient outcome between private and public hospitals. Finally, the median daily costs of non-survivor patients were higher than survivors during ICU stay.     

Factors influencing the length of hospitalisation in intensive care units: a prospective observational study

INTRODUCTION: The length of stay (LOS) in patients admitted to intensive care units (ICUs) is influenced by the clinical history of the patient, so the main factors affecting clinical outcome are logical candidates to be predictors of LOS. Since there is still limited information about which factors can influence LOS in these patients, we undertook this observational study in Italian hospitals. MATERIALS AND METHODS: From 1 August to 31 October 2001 we enrolled a maximum of 10 consecutive patients admitted to ICUs in 16 Italian hospitals. The following information was recorded from each patient: date of admission; APACHE II score on admission; active sepsis and/or septic shock on admission; sepsis and/or septic shock developed during the stay in ICU; Glasgow coma scale on the third day; date and clinical outcome upon discharge from the hospital (alive or dead). RESULTS: In the study 131 patients were enrolled; 31 (23.7%) had active sepsis upon admission to ICU and 10 (7.6%) had septic shock; 12 (9.2%) developed sepsis during hospitalization and 12 (9.2%) developed septic shock. At the end of the study, 101 patients were alive and 30 had died. The overall mean LOS was 12 days. The mean LOS was 18.3 days for the subgroup with sepsis and 8.3 days in the subgroup without sepsis. Sepsis was the only factor that significantly influenced the LOS (P = 0.016). CONCLUSIONS: Our study was aimed to analyse the factors that influence the LOS in ICU patients and found that among the variables that affected LOS, sepsis had the greatest impact. Other studies had evaluated the impact of some variables on LOS and identified sepsis and infection as a determinant prolonging LOS.     

Time to Administration of Antibiotics among Inpatients with Severe Sepsis or Septic Shock

Background

Current evidence suggests that administration of appropriate antibiotic therapy within 1 h after the onset of hypotension significantly improves mortality rates among patients with severe sepsis and septic shock.

Objectives:

To determine the interval from recognition of severe sepsis or septic shock in inpatients to initial administration of antibiotic and to assess institutional compliance with the Surviving Sepsis Campaign’s recommendation for early antibiotic therapy.

Methods:

A 6-month retrospective chart analysis was conducted to determine the interval from documented onset of hypotension to initial administration of antibiotic for patients with severe sepsis or septic shock. Patients who were admitted to a general medicine ward, a surgery ward, or the intensive care unit (ICU) of a 475-bed university-affiliated hospital and who met the criteria for severe sepsis or septic shock were eligible for inclusion. Patients who received antibiotics before meeting the criteria for severe sepsis or septic shock were excluded.

Results:

Charts for 100 patients with severe sepsis or septic shock were reviewed. The mean age was 69.0 years (standard deviation 18.7 years), and 56% were men. The median interval from onset of severe sepsis or septic shock to administration of antibiotic was 4.00 h (interquartile range [IQR] 1.80–6.45 h). The median interval from the time a physician ordered an antibiotic to administration of the drug was 1.28 h (IQR 0.57–3.05 h). The interval between ordering and administration differed significantly for patients on the wards (5.67 h), those with onset in the ICU (4.00 h), and those with onset in the emergency department (3.28 h) (p = 0.039). The overall survival rate was 56%.

Conclusion:

At the study hospital, the interval from onset of severe sepsis or septic shock to initial administration of antibiotic to inpatients exceeded the 1-h period recommended by the Surviving Sepsis Campaign. These results will be used as a baseline for future quality assurance and improvement initiatives aimed at minimizing the time to antibiotic administration for this group of patients, who are at high risk of death.     

Severe community acquired pneumonia: a one-year analysis in a tertiary referral intensive care unit

AIMS: To define outcomes, characteristics, microbiology and salient prognostic factors of patients admitted to our intensive care unit (ICU) with severe community acquired pneumonia, over a one year period. METHODS: All adult patients with severe community acquired pneumonia admitted between July 1997 and July 1998 were studied. Data were extracted by retrospective chart review. Variables assessed included underlying conditions and baseline physical parameters. Evolutionary variables eg, septic shock and laboratory data including microbiology and arterial blood gas determinants were also assessed. Prognostic factors were determined by comparison of the above variables between survivors and non-survivors. The prognostic value of the British Thoracic Society discriminant 'rule one' was assessed. Results. 32 patients were assessed. ICU mortality was 31%. 84% of patients had co-morbidity. The average age was 58.5 (SD 17.4) years and the average APACHE 11 score was 20.37 (SD 9.12). A microbiological diagnosis was made in 40%. Mortality was not increased in those in whom a bacterial diagnosis was not made. Commonest pathogens isolated were Streptococcus pneumoniae (46%), gram negative organisms (29%) and Staphylococcus aureus (23%). Prognostic factors on and during ICU admission were the need for mechanical ventilation (p=0.0003), septic shock (p=0.02), inotrope requirement (p=0.003), low serum albumin (p=0.041), base deficit (p=0.04), INR (p=0.02) and inspired oxygen concentration (p=0.003). On initial admission to hospital the presence of bilateral pneumonia was the only variable correlated with outcome (p=0.01). The British Thoracic Society 'rule one' did not correlate with death either on admission to hospital or ICU. CONCLUSIONS: Severe community acquired pneumonia carries a high mortality despite ICU management. Bacterial diagnostic rate was low but made no difference to mortality. Streptococcus pneumoniae was the commonest causative pathogen. The development of septic shock, requirement for mechanical ventilation and bilateral disease are important adverse prognostic indicators.     

硝酸甘油治疗脓毒性休克患者效果的影响因素分析

目的 分析硝酸甘油治疗脓毒性休克患者效果的影响因素.方法 回顾性选取2014年至2015年在本院重症医学科住院并接受硝酸甘油治疗的脓毒性休克患者为研究对象,以乳酸清除率为因变量,以基线各参数为自变量进行多因素Logistic回归分析.结果 多因素Logistic回归分析显示,对乳酸清除率的独立影响因素有初始血乳酸(OR=1.68,95％CI:1.25-5.93,P＜0.05)、中心静脉血氧饱和度(OR=2.85,95％CI:1.67-8.42,P＜0.05)、动脉与脉搏氧饱和度差值(OR=4.65,95％CI:2.32-11.67,P＜0.05).结论 基线乳酸水平较高、中心静脉血氧饱和度异常升高、动脉与脉搏氧饱和度差值增大的脓毒性休克患者硝酸甘油治疗有效.     

Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have increasingly replaced tricyclic antidepressants (TCAs) in the treatment of depression. They appear to be safer in overdose, but there is little information on their spectrum of toxicity in overdose, or relative toxicity of each agent. Objective: To determine the effect of SSRIs in overdose, as a group, and the relative toxicity of five different SSRIs. METHODS: A review of consecutive SSRI poisoning admissions to a single toxicology unit. Outcomes examined were length of stay [LOS], intensive care [ICU] admission rate, coma, seizures, electrocardiographic [ECG] abnormalities, and presence of serotonin syndrome [SS]. Logistic regression was used to model the outcome QTc >440 msec. RESULTS: There were 469 SSRI poisoning admissions analyzed after exclusions. The median LOS for all SSRI overdose admissions was 15.3 h (IQR: 10.5-21.3) and 30 of 469 (6.4%; 95% CI 4.3-9.0%) cases were admitted to ICU. The incidence of seizures was 1.9% and coma was 2.4%. Serotonin syndrome occurred in 14% of overdoses. Comparison of median QTc intervals of the five SSRIs was significantly different (p=0.0002); citalopram (450 IQR: 436-484) was individually different to fluoxetine (p=0.045), fluvoxamine (p=0.022), paroxetine (p=0.0002), and sertraline (p=0.001). The proportion of citalopram overdoses with a QTc >440 msec was 68%, differing significantly from sertraline (adjusted OR: 5.11 95% CI 2.32-11.27). Comparison of median QT intervals of the five SSRIs was statistically different (p=0.026); citalopram (400 IQR: 380-440) was individually different from sertraline (p=0.023). CONCLUSIONS: This study shows SSRIs are relatively safe in overdose despite serotonin syndrome being common. The exception was citalopram, which was significantly associated with QTc prolongation. We believe that cardiac monitoring should be considered in citalopram overdose, particularly with large ingestions and patients with associated cardiac disease.     

Bioactivity of enoxaparin in critically ill patients with normal renal function

Aim

In critically ill patients, reduced anti-FXa plasma activity following subcutaneous administration of enoxaparin or nadroparin has been described. In this study, we aimed to investigate the bioactivity of enoxaparin in critically ill patients and controls.

Methods

A prospective, controlled, open label study was performed on a medical intensive care unit (ICU) and a general medical ward. Fifteen ICU patients (male = 12, median age 52 years [IQR 40−65], with a median Simplified Acute Physiology Score of 30 [IQR 18−52]) and sex- and age-matched medical ward patients were included. The anti-FXa plasma activity was measured after a single subcutaneous dose of 40 mg enoxaparin. The thrombus size of a clot formed in an ex vivo perfusion chamber and endogenous thrombin potential (ETP) were measured.

Results

The anti-FXa plasma activity increased significantly after enoxaparin administration, with peak levels at 3 h after treatment, but was comparable between the ICU and medical ward groups (median 0.16 IU ml⁻¹[IQR 0−0.22 IU ml⁻¹]vs. 0.2 IU ml⁻¹[IQR 0.15−0.27 IU ml⁻¹], respectively, P= 0.13). The area under the anti-FXa activity curve from 0–12 h was similar between the groups (median 0.97 IU ml⁻¹ h [IQR 0.59−2.1] and 1.48 IU ml⁻¹ h¹[IQR 0.83−1.62], P= 0.42 for the ICU group compared with the control group, respectively). The ETP was lower in the ICU group (P < 0.05) at baseline, but it was comparable at 3 h between the groups. Thrombus size decreased at 3 h compared with predose (P= 0.029) and was not different between the groups.

Conclusion

Similar bioactivity was achieved with a standard dose of subcutaneous enoxaparin in this selected cohort of ICU and general ward patients with normal renal function.     

Therapeutic drug monitoring of vancomycin in severe sepsis and septic shock

BACKGROUND: The sudden changes (increase in capillary permeability, edema formation, vasodilation and hypotension) observed in septic patients and the measurements taken in order to revert this situation make vancomycin concentrations difficult to interpret. Therapeutic drug monitoring (TDM) of vancomycin is routinely performed at steady state, target concentrations are peaks between 20 and 40 mg/l and troughs of 5-10 mg/l. Lately, continuous infusion of vancomycin (CIV) has been used as an alternative mode of administration mainly in critically ill patients with sepsis or septic shock. Despite this novel mode of administration, the need of drug monitoring in this population is under discussion. OBJECTIVE: The aim of our study was to test the usefulness of a multi-compartment model in order to understand the rapid changes that occur in critically ill patients. MATERIALS AND METHODS: A prospective, cohort study was carried out in the intensive care unit of the University Hospital. 25 intensive care unit adults patients with severe sepsis or septic shock receiving vancomycin in CIV modality for documented gram-positive infections were included in the study. Once the infusion was started, blood samples were drawn periodically and analyzed by fluorescence polarisation immunoassay (FPIA, TDx, Abbott Laboratories, Chicago, IL, USA). A multi-compartment model was used to predict vancomycin level evolution throughout the treatment of patients with sepsis. RESULTS: High doses of vancomycin were administered in order to rescue patients from septic shock. Plasma drug concentration dropped while clinical condition of patients worsened. Conversely, drug levels increased spontaneously once the infection was reverted. The theoretical model provided greater insight into pharmacokinetic features related with the use of vancomycin in septic patients. CONCLUSIONS: There was consistency between the model based prediction and the experimental data so dose adjustment was performed in order to reach target concentrations above 20 mg/l and an initial dose of 3 grams of vancomycin per day was recommended to reach these levels.     

胺碘酮静脉给药治疗心房纤维颤动患者引致休克的临床特点

目的：探讨胺碘酮静脉给药治疗心房纤维颤动患者引起休克的临床特点。方法：收集2003年至2007年中文医学文献关于胺碘酮静脉给药治疗心房纤维颤动患者引致休克的临床资料，包括患者的基础心脏病，心房纤维颤动发作时的心律、心率、血压、心功能状态、心电图以及胺碘酮的用法用量。对胺碘酮输液的浓度、静脉滴注速度和总剂量以及休克发生的时间、表现和处理进行分析。结果：共收集7例胺碘酮所致休克患者的临床资料，其中2例来自本院。胺碘酮溶于5％葡萄糖注射液100ml中，浓度为1．5～7．5mg／ml，静脉给药速度为2．5～10mg／min。用药后休克发生的时间，4例为2min内，3例为5～20min内，持续时间为3～120min。2例休克患者伴有意识障碍，5例患者休克时仍有心房纤维颤动。结论：胺碘酮静脉给药可能引起休克，临床表现危重，及时对症治疗可缓解。     

阿托伐他汀钙在老年脓毒性休克患者炎症控制中的作用

目的 探讨阿托伐他汀钙在老年脓毒性休克患者炎症控制中的作用。方法 采用前瞻性随机对照研究的方法,将2019年1月—2019年12月宁波市医疗中心李惠利医院东部院区重症医学科（intensive care unit,ICU）收治的老年脓毒性休克患者,随机分为他汀组和对照组,对照组采用常规综合支持治疗,他汀组在对照组的基础上加用阿托伐他汀钙。记录2组患者的年龄、性别、病因、急性生理学与慢性健康状况评分Ⅱ（APACHE Ⅱ）等基本资料;观察并记录患者治疗前及治疗后第1天、第3天、第7天的C反应蛋白、前降钙素、体温波动、白细胞计数、中心静脉-动脉二氧化碳分压差[P_（v-a）CO₂,GAP]和中心静脉-动脉二氧化碳分压差/动脉-中心静脉氧含量差[P_（v-a）CO₂/C_（a-v）O₂,GAP ratio]等临床指标;记录2组患者28 d存活率、机械通气时间、ICU平均住院时间、总住院天数等预后指标。结果 最终研究纳入86例患者,2组基本资料差异无统计学意义。在治疗前和治疗后第1天,2组临床指标对比无差异;在治疗后第3,7天,他汀组临床指标的改善均优于对照组（P<0.05）;并且随着时间的推移,2组不同组间与检测时间点对各临床指标的改善均存在交互作用（P<0.05）,提示越早应用阿托伐他汀钙,患者临床指标的改善越明显。2组预后对比,他汀组患者28 d存活率、机械通气时间、ICU平均住院和总住院时间均优于对照组。结论 应用阿托伐他汀钙可以改善老年脓毒性休克患者的炎症和全身灌注情况,可提高患者28 d存活率,减少机械通气时间、ICU平均住院时间和总住院时间,且越早应用获益越多。     

不同热卡供给对脓毒性休克100例预后的影响

目的 比较不同热卡供给对脓毒性休克病人预后的影响,以期为脓毒性休克病人提供最佳热卡供给。方法 采用回顾性分析方法,选取山西医科大学第一临床医学院2019年8月至2021年8月符合纳入标准的100例脓毒性休克病人行营养支持治疗的临床资料,将病人按非蛋白热卡供给量分为A组、B组2组。A组喂养方式为渐进式喂养,入ICU第3天热卡达到目标热卡的70%,逐渐增加热卡到第7天达到目标热卡。B组喂养方式为等热卡喂养,入ICU第3天达到目标热卡,第3天到第7天目标热卡喂养。两组入院时一般资料相近,蛋白提供量相似。分别记录两组病人每日热卡供给量、蛋白供给量,第1天及第7天营养指标、肝肾功、血糖、胰岛素用量,记录住院期间机械通气时间、住院时间、住ICU时间、院内感染率、ICU病死率、28 d病死率等并进行比较。探讨热卡供给量与脓毒性休克病人预后的关系。结果 两组给予7 d营养支持后,A组的胰岛素用量少于B组[20.00(0.00,50.00)IU比50.00(0.00,70.00)IU],A组的机械通气时间比B组短[（7.69±6.80）d比（12.44±14.02）d],A组的住院时间比B组短[（18....     

Impact of prophylactic amiodarone on length of hospital stay, stroke, and atrial fibrillation after cardiothoracic surgery

STUDY OBJECTIVE: To evaluate the effect of prophylactic amiodarone on length of stay (LOS), postoperative stroke, and postoperative atrial fibrillation (POAF). DESIGN: Retrospective cohort study. SETTING: Hartford Hospital, Hartford, Connecticut. PATIENTS: Two thousand forty-six patients who underwent cardiothoracic surgery from February 1998-October 2003 (186 received amiodarone, 1860 were controls). MEASUREMENTS AND MAIN RESULTS: Patients receiving any of the prophylactic amiodarone regimens used in the Atrial Fibrillation Suppression Trials (AFIST) I and II were matched (1:10 matching) for age, valvular surgery, history of atrial fibrillation, sex, beta-blocker intolerance, and preoperative digoxin therapy with patients not receiving amiodarone prophylaxis. The AFIST regimens consisted of oral amiodarone 6 g over 6 days and 7 g over 10 days, beginning on preoperative days 1 and 5, respectively, or a hybrid intravenous and oral loading regimen delivering amiodarone 7 g over 5 days. Mean+/-SD age of the patients was 68.9+/-9.8 years, 75% were men, and 21% had undergone valvular surgery. Patients receiving prophylactic amiodarone had a shorter LOS (8.6+/-6.0 days) than controls (11.6+/-14.0 days, p=0.003) and a reduced frequency of POAF (23.1% vs 29.9%, p=0.05). Frequency of stroke was not significantly affected (2.2% vs 2.7% in the amiodarone vs control groups, p=0.61). CONCLUSION: Use of the prophylactic amiodarone regimens from the AFIST trials reduced LOS by 3.0 days and frequency of POAF by 22.7%.     

Impact of pharmaceutical care on pain and agitation in a medical intensive care unit in Thailand

Background Currently, a lack of pharmaceutical care exists concerning pain and agitation in medical intensive care units (MICU) in Thailand. Pharmaceutical care focusing on analgesics/sedatives would improve clinical outcomes. Objective To investigate the impact of pharmaceutical care of pain and agitation on ICU length of stay (LOS), hospital LOS, ventilator days and mortality. Setting The MICU of a university hospital. Method A before/after study was conducted on mechanically ventilated patients receiving analgesics/sedatives. Medical chart reviews and data collection were conducted in the retrospective group (no pharmacists involved). In the prospective group, pharmacists involved with the critical care team helped select analgesics/sedatives for individual patients. Main outcome measure ICU LOS Results In total, 90 and 66 patients were enrolled in retrospective and prospective groups, respectively. The median duration of ICU LOS was reduced from 10.00 (2.00–72.00) in the retrospective group to 6.50 days (2.00–30.00) in the prospective group (p = 0.002). The median hospital stay was reduced from 30.50 days (2.00–119.00) in the retrospective group to 17.50 days (2.00–110.00) in the prospective group (p < 0.001). Also, the median ventilator days was reduced from 14.00 days (2.00–90.00) to 8.50 days (1.00–45.00), p = 0.008. Mortality was 53.03% in the prospective group and 46.67% in the retrospective group (p = 0.432). Conclusion Pharmacist participation in a critical care team resulted in a significant reduction in the duration of ICU LOS, hospital LOS and ventilator days, but not mortality.     

Changes in medication regimen complexity index following medication-related hospital admissions: A retrospective single-centre study

BackgroundMedication-related hospitalisations present an opportunity for de-prescribing and simplification of medication regimens. The Medication Regimen Complexity Index (MRCI) is a tool for measuring the complexity of medication regimens.ObjectivesTo evaluate whether MRCI changes following medication-related hospitalisations, and to evaluate the relationship between MRCI, length of stay (LOS) in hospital, and patient characteristics.MethodsA retrospective medical record review of patients admitted to a tertiary referral hospital in Australia for medication-related problems, January 2019 to August 2020. MRCI was calculated using pre-admission medication lists and discharge medication lists.ResultsThere were 125 patients who met inclusion criteria. The median (IQR) age was 64.0 years (45.0–75.0) and 46.4% were female. Median MRCI decreased by 2.0 following hospitalisation: from median (IQR) 17.0 (7.0–34.5) on admission vs 15.0 (3.0–29.0) on discharge (p < 0.001). Admission MRCI predicted LOS ≥2 days (OR 1.03, 95%CI 1.00–1.05, p = 0.022). Allergic reaction-related hospitalisations were associated with lower admission MRCI.ConclusionsThere was a decrease in MRCI following medication-related hospitalisation. Targeted medication reviews for high-risk patients (e.g., those with medication-related hospitalisations) could further reduce the burden of medication complexity following discharge from hospital and possibly prevent readmissions.     

Uncomplicated Streptococcal Bacteremia: The Era of Oral Antibiotic Step-down Therapy?

BackgroundThe purpose of this study was to compare the clinical outcomes of adults with uncomplicated streptococcal bacteremia who received either oral (PO) step-down or continued intravenous (IV) therapy.MethodsThis was a retrospective, single-center, cohort study, including adults admitted with Streptococcal bloodstream infection between January 1, 2013, and December 31, 2020. Only patients with uncomplicated Streptococcal bloodstream infections were included. Patients who transitioned to PO therapy within 5 days from bacteremia onset were compared to patients receiving continued IV therapy. The primary outcome was clinical failure, defined by either 90-day hospital readmission or mortality. Secondary outcomes included hospital length of stay (LOS) and antibiotic-related adverse events (AAEs).ResultsOf the 264 patients included, 42% were transitioned to PO therapy. Group B Streptococcus (22.7%) was the most common isolate. The most common sources of infection were skin and soft tissue (35%) and pulmonary (25%). Intensive care unit (ICU) stay was more common in the continued IV therapy group (22.2%) than in the PO step-down group (5.4%). The frequency of clinical failure was similar in the IV and PO groups (24.2% vs. 18.0%, P=0.23). The IV group had longer hospital LOS (median, [interquartile range (IQR)]) compared with the PO group (7 [5-13.5] vs. 4 [3], [4], [5] days, P<0.001). The incidence of AAEs was similar in the IV and PO groups (1.3% vs. 1.8%, P=0.74).ConclusionOral antibiotic step-down therapy may be appropriate for the treatment of uncomplicated Streptococcal bacteremia, with consideration of factors such as patient comorbidities, type of infection, source control and clinical progress.     

Pharmacokinetics of intravenous and oral levofloxacin in critically ill adults in a medical intensive care unit

STUDY OBJECTIVE: To characterize the pharmacokinetic disposition of intravenous and oral levofloxacin in critically ill adults. DESIGN: Prospective, open-label study. SETTING: University teaching hospital. PATIENTS: Thirty critically ill patients in a medical intensive care unit (ICU). INTERVENTIONS: All patients received levofloxacin as part of their routine medical care. Pharmacokinetic evaluations were performed in 28 patients receiving intravenous levofloxacin. Ten of these patients subsequently were switched to oral levofloxacin and underwent a second pharmacokinetic evaluation during oral therapy. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD levofloxacin half-life, clearance at steady state, and volume of distribution in all 28 patients were 8.0 +/- 1.7 hours, 134 +/- 35 ml/minute, and 1.2 +/- 0.3 L/kg, respectively Maximum and minimum serum concentrations (Cmax and Cmin) and area under the serum concentration-time curve from 0-24 hours (AUC(0-24)) in patients receiving levofloxacin 500 mg intravenously were 7.5 +/- 0.8 mg/L, 1.0 +/- 0.5 mg/L, and 66.1 +/- 15.7 mg x hour/L, respectively Observed Cmax, Cmin, and time at which maximum concentration was achieved after oral doses of levofloxacin 500 mg were 5.5 +/- 1.1 mg/L, 0.8 +/- 0.4 mg/L, and 1.3 +/- 0.4 hours, respectively. These values were significantly different (p < 0.05) from those observed after intravenous dosing in the same patients; other pharmacokinetic parameters were similar. Statistically significant increases (p < 0.05) in Cmax, Cmin, half-life, and AUC(0-24) were found in critically ill patients administered multiple doses of intravenous levofloxacin compared with historical data from healthy volunteers. CONCLUSIONS: The dosage regimen of intravenous levofloxacin 500 mg once/day appears adequate for most pathogens found in critically ill patients with normal renal function. Less susceptible pathogens may require an increased daily dose for more optimal therapy. Orally administered levofloxacin appears to be well absorbed in selected ICU patients and has pharmacokinetics similar to those of intravenously administered levofloxacin.     

Cost-effectiveness of amiodarone for prophylaxis of atrial fibrillation in coronary artery bypass surgery.

The cost-effectiveness of amiodarone prophylaxis of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) was determined. A decision analysis using current hospital data and values from the literature was conducted. Under the base-case scenario, CABG patients received usual care (no prophylaxis) or 2 g of oral amiodarone hydrochloride over one to three days before surgery and 400 mg daily for seven days after surgery. Costs of hospitalization in the intensive care unit (ICU) and the cardiac step-down unit (SDU), cardioversion costs, electrocardiogram costs, drug costs, nursing administration charges, and pharmacy i.v. admixture charges were included. A sensitivity analysis using a Monte Carlo simulation and a one-way sensitivity analysis were performed. The mean cost per AF event avoided was lower in the amiodarone group ($15,750, 95% confidence interval [CI]: $15,591-$15,999) than the control group ($17,426,95% CI: $17,252-$17,600). A majority of the cost difference was due to the cost of hospitalization for patients without AF, the frequency of AF, and the cost of hospitalization in the SDU for patients with AF. For patients treated with amiodarone who did not develop AF, the cost difference was sensitive to changes in the cost of hospitalization and the efficacy of amiodarone. For patients who did develop AF, the cost difference was robust. Prophylaxis of AF with amiodarone in CABG patients was more cost-effective than usual care in the short term from a hospital perspective; the results were sensitive to changes in the cost of hospitalization of patients who did not develop AF and the efficacy of amiodarone.     

Amiodarone for rapid cardioversion of chronic atrial tachyarrhythmia?

Electrical cardioversion of atrial tachyarrhythmia has disadvantages, such as the need for general anaesthesia, skin burns and thoracic pain. Pharmacodynamic cardioversion is without these side effects, but the reports of the efficacy of the treatment vary a lot. Amiodarone has been the only drug so far reported to give a combination of high efficacy and low frequency of serious side effects such as ventricular tachycardia and shock. The purpose of the present study was to assess the effect of amiodarone on chronic atrial tachycardia. Seventeen patients with chronic atrial fibrillation or flutter were given an oral dose of 30 mg/kg amiodarone. Serial blood tests after amiodarone ingestion were taken to document absorption. Patients, who did not convert to sinus rhythm within 24 hr were treated by electrical cardioversion. No patients converted pharmacodynamically to sinus rhythm. Twelve patients (71%) reached the recommended serum concentration of amiodarone (2-2.5 mg/l, median 2.4 mg/l, range 0.96-4.7). The concentration of desethylamiodarone remained low (<0.2 mg/l), and there were no objective or subjective side effects following the treatment. Sixteen patients (94%) were converted to sinus rhythm the day after by electrical cardioversion without complications. A single high dose of amiodarone is a safe but ineffective method of converting chronic atrial fibrillation and flutter, and may be used as adjuvant therapy in combination with electrical cardioversion.