Fixed dose ketamine for prehospital management of hyperactive delirium with severe agitation.

INTRODUCTION: Patients exhibiting signs of hyperactive delirium with severe agitation (HDSA) may require sedating medications for stabilization and safe transport to the hospital. Determining the patient's weight and calculating the correct weight-based dose may be challenging in an emergency. A fixed dose ketamine protocol is an alternative to the traditional weight-based administration, which may also reduce dosing errors. The objective of this study was to evaluate the frequency and characteristics of adverse events following pre-hospital ketamine administration for HDSA. METHODS: Emergency Medical Services (EMS) records from four agencies were searched for prehospital ketamine administration. Cases were included if a 250 mg dose of ketamine was administered on standing order to an adult patient for clinical signs consistent with HDSA. Protocols allowed for a second 250 mg dose of ketamine if the first dose was not effective. Both the 250 mg initial dose and the total prehospital dose were analyzed for weight based dosing and adverse events. RESULTS: Review of 132 cases revealed 60 cases that met inclusion criteria. Patients' median weight was 80 kg (range: 50-176 kg). No patients were intubated by EMS, one only requiring suction, three required respiratory support via bag valve mask (BVM). Six (10%) patients were intubated in the emergency department (ED) including the three (5%) supported by EMS via BVM, three (5%) others who were sedated further in the ED prior to requiring intubation. All six patients who were intubated were discharged from the hospital with a Cerebral Performance Category (CPC) 1 score. The weight-based dosing equivalent for the 250 mg initial dose (OR: 2.62, CI: 0.67-10.22) and the total prehospital dose, inclusive of the 12 patients that were administered a second dose, (OR: 0.74, CI: 0.27, 2.03), were not associated with the need for intubation. CONCLUSION: The 250 mg fixed dose of ketamine was not >5 mg/kg weight-based dose equivalent for all patients in this study. Although a second 250 mg dose of ketamine was permitted under standing orders, only 12 (20%) of the patients were administered a second dose, none experienced an adverse event. This indicates that the 250 mg initial dose was effective for 80% of the patients. Four patients with prehospital adverse events likely related to the administration of ketamine were found. One required suction, three (5%) requiring BVM respiratory support by EMS were subsequently intubated upon arrival in the ED. All 60 patients were discharged from the hospital alive. Further research is needed to determine an optimal single administration dose for ketamine in patients exhibiting signs of HDSA, if employing a standardized fixed dose medication protocol streamlines administration, and if the fixed dose medication reduces the occurrence of dosage errors.

A cost comparison of pembrolizumab: Fixed and weight-based dosing.

BACKGROUND: Pembrolizumab, an immune checkpoint inhibitor, indicated to treat multiple cancers, was initially approved in Australia as weight-based dosing at 2 mg/kg every 3 weeks (Q3W). Subsequent approvals used 'fixed' dosages of 200 mg Q3W or 400 mg every 6 weeks (Q6W). Pharmacokinetic equivalence was demonstrated between dosing strategies, with no significant differences in efficacy or toxicity. Fixed dosing regimens are routinely used in Australia. AIM: To model and compare the cost of weight-based dosing of pembrolizumab to standard fixed dosing regimens. METHOD: A single centre, retrospective review was conducted. Patients, identified from dispensing software, who commenced on pembrolizumab between January and December 2022 were included. Patient demographic and treatment data was extracted from electronic medical records. Costs of weight-based doses were calculated and compared to the cost of fixed dosing. Variables such as acquisition cost, funding mechanisms and 'vial sharing' were considered. RESULTS: Fifty-two patients were included (63% male, median age 68 years). Of the 211 doses of pembrolizumab administered (average 4.1 doses/patient), 161 were Q3W doses, and 50 were Q6W doses. The acquisition cost for a fixed 200 mg and 400 mg dose was $7646, and $15,292, respectively. The average patient weight was 77.6 kg (SD 19 kg), which equated to $5933 for a weight-based Q3W dose, and $11,867 for the Q6W dose; a potential cost avoidance of $1965 and $3930 per dose, respectively. This represented a possible 23.5% avoidance in medication acquisition cost. Over the study period of 1 year, using weight-based dosing for pembrolizumab had the potential to reduce medication expenditure by $467,996. DISCUSSION: Significant cost avoidance could be achieved via weight-based pembrolizumab dosing. Given the substantial total cost of pembrolizumab, the growing number of indications and the expected equivalent treatment outcomes with weight-based pembrolizumab, the potential cost reductions of weight-based pembrolizumab at both institution and government level should be further explored.

Weight-based oxytocin infusion for preventing uterine atony during caesarean delivery in non-labouring patients: A dose-response study.

Postpartum haemorrhage remains a significant cause of maternal morbidity and mortality with the commonest reason being uterine atony. For prevention of uterine atony during caesarean delivery, oxytocin is advocated as a first line drug. There is however no published data regarding utility of a weight-based oxytocin infusion. The present study evaluated dose-response relationship for oxytocin infusion when used as weight-based regimen. A total of 55 non-labouring patients without risk factors for uterine atony and scheduled for caesarean delivery under spinal anaesthesia were enrolled. Randomization was done to receive oxytocin infusion in a dose of 0.1, 0.15, 0.2, 0.25 or 0.3 IU kg-1  h-1 (n = 11 each), initiated at the time of cord clamping and continued until the end of surgery. Successful outcome was defined as attaining an adequate uterine response at 4 min of initiation of infusion and maintained till end of surgery. Oxytocin associated hypotension, tachycardia, ST-T changes, nausea/vomiting, flushing and chest pain were also observed. A significant linear trend for adequate intraoperative uterine tone was seen with increasing dose of weight-based oxytocin infusion (P < 0.001). The effective dose in 90% population (ED90) was 0.29 IU kg-1  h-1 (95% CI = 0.25-0.42). Amongst the oxytocin associated side effects, a significant linear trend was seen between increasing dose of oxytocin infusion and hypotension as well as nausea/vomiting (p = 0.016 and 0.023 respectively). Thus, oxytocin infusion during caesarean delivery may be used as per the patient's body weight.

Establishing dose bands for commonly prescribed oral medications for children in the UK: Results of a Delphi study.

OBJECTIVE: To establish weight-based dose bands for commonly used oral medicines, given in liquid forms, for children in the UK that could be used for prescribing and administering accurate and safe drug doses. METHODS: A list of commonly prescribed, oral liquid medications was established from the medication dispensing database of four UK hospitals and a primary care database. The evidence base of currently used dose regimens for each drug was identified from paediatric reference books, summary of product characteristics and the literature. Then, weight-based dose bands were developed and a modified Delphi process was used to achieve healthcare professional consensus about the suggested dose bands for each drug. RESULTS: Forty-six experts in paediatric medicines participated in the Delphi process (mean years of experience 17.3 ± 9.4 [standard deviation]) and assessed 45 oral liquid drugs in total. Four categories of weight-based dose bands were established: drugs with two dose bands (17.8%, 8/45), drugs with three dose bands (64.4%, 29/45), drugs with four dose bands (15.6%, 7/45) and drugs with five dose bands (2.2%, 1/45). The 46 participants reached consensus on all the suggested dose bands for 53.3% (24/45) of the drugs. Consensus was reached in the first round of the Delphi process for 91.7% (22/24) of the drugs and after two rounds for two drugs. No agreement was achieved on any of the suggested dose bands for 26.7% (12/45) of the drugs. CONCLUSION: This study provides healthcare professionals with a set of recommended weight-based dose bands for commonly prescribed oral liquid drugs for children. These bands could establish the basis for change in clinical practice to reduce dosing errors and improve healthcare for children.

Safety, tolerability, and pharmacokinetics of weight-based IV loading dose of lacosamide in the ICU.

Among the newer antiseizure medications, lacosamide (LCM) has been increasingly used for acute seizures and status epilepticus in intensive care unit (ICU). We reviewed retrospectively weight-based dosing of IV LCM in patients admitted to ICU with acute seizures and status epilepticus. We have analyzed 354/382 patient treated with IV LCM in ICU during the years 2013-2016. Data collected were age, total body weight, body mass index (BMI), loading dose, post-IV infusion LCM blood level, duration of infusion, blood pressure, heart rate, oxygen saturation, mean arterial pressures, and documented initiation of pressor agents during or within in 30 min of infusion. Larger doses >8 mg/kg of IV LCM that can be safely administered in ICU patients produce effective plasma levels of 15-20 µg/ml with relatively constant volume of distribution.

Intravenous Ketamine for Cancer Pain: A Single-Center Retrospective Analysis Comparing Fixed-Rate Versus Weight-Based Dosing.

Although weak evidence exists to support subanesthetic ketamine for cancer pain treatment, successful use may be hindered in the absence of standardized dosing guidance. We aimed to compare the success rates of intravenous ketamine fixed-rate versus weight-based dosing strategies for cancer pain treatment, and to assess patient characteristics that correlate with treatment success. We conducted a single-center retrospective review including non-critically ill adults with cancer pain who received subanesthetic ketamine for at least 24-h. All patients received fixed-rate ketamine; weight-based doses were retrospectively determined using total body weight. Treatment was considered successful if after reaching the maximum prescribed ketamine dose the patient had a 30% reduction in: baseline pain score, as-needed opioid use, or total morphine equivalent daily dose over a standardized 24-h. Of 105 included patients, 51 (48.6%) successfully responded to ketamine. Responders had lower fixed-rate ketamine doses compared to non-responders (median[IQR] 15 mg/hr[10-15] vs. 15 mg/hr[15-20], p = 0.043), but no difference in retrospectively calculated weight-based doses (0.201 ± 0.09 mg/kg/hr vs. 0.209 ± 0.08 mg/kg/hr, p = 0.59). Responders had higher daily opioid requirements at baseline compared to non-responders (p = 0.04). Though underpowered, our findings suggest that weight-based ketamine dosing may not convey additional benefit over fixed-rate dosing.

Comparative Effectiveness and Safety of Standard-Dose and Low-Dose Pembrolizumab in Patients with Non-Small-Cell Lung Cancer: A Multi-Institutional Cohort Study in Taiwan.

Fixed doses at 200 mg of pembrolizumab or 2 mg/kg every 3 weeks are the standard dosages for first- and second-line treatment of non-small-cell lung cancer (NSCLC); however, in clinical practice, patients with NSCLC may receive lower doses of pembrolizumab due to drug product availability or economic factors. To date, the comparative effectiveness and safety of the standard dose and lower doses of pembrolizumab in these patients still remains limited. We conducted a retrospective cohort study by analyzing electronic medical records data from the largest multi-institutional hospital system in Taiwan. Advanced NSCLC patients newly receiving pembrolizumab with or without chemotherapy were included. Patients were classified into: (1) the standard-dose group (≥2 mg/kg), and (2) the low-dose group (<2 mg/kg). We applied inverse probability of treatment weighting (IPTW) to compare the overall survival (OS) and immune-related adverse events (irAEs) between the two treatment groups, and to evaluate the minimum clinically effective dose of pembrolizumab. We included a total of 147 NSCLC patients receiving standard-dose pembrolizumab (mean [range] age: 63.7 [58.0−73.0] years; male: 62.6%; mean [range] body weight: 60.5 [58.0−73.0] kg) and 95 patients receiving low-dose pembrolizumab (mean [range] age: 62.0 [50.0−68.8] years; male: 64.2%; mean [range] body weight: 63.9 [55.0−73.8] kg). After IPTW adjustments, the median OS was similar for both the standard-dose and low-dose pembrolizumab groups (19.3 vs. 14.3 months, log-rank p = 0.15). Also, the rate for all classes of irAEs was similar for both groups. We found that patients with a pembrolizumab dose ≥1.8 mg/kg were associated with better OS than those receiving <1.8 mg/kg. Our findings suggested no significant difference in OS and irAEs between patients receiving pembrolizumab ≥2 mg/kg and <2 mg/kg in clinical practice. A pembrolizumab dose ≥1.8 mg/kg may be the clinically most efficient dose.

Efficacy of Single Low-Dose Rasburicase in Management of Tumor Lysis Syndrome in Leukemia and Lymphoma Patients.

BACKGROUND: Tumor lysis syndrome (TLS) is a metabolic emergency in hematology patients. The recommended dose of rasburicase for the management of TLS is 0.2 mg/kg per day for 5 days, which is cost prohibitive for many patients. We sought to determine the efficacy of single low-dose rasburicase in the prevention and treatment of hyperuricemia in TLS. PATIENTS AND METHODS: We planned a prospective study for the safety and efficacy of fixed (weight based) dose of rasburicase to manage TLS. Patients diagnosed with leukemia/lymphoma with laboratory or clinically confirmed TLS or presence of ≥ 2 high-risk factors and serum uric acid > 7.5 mg/dL were included. The primary endpoint was uric acid normalization (< 7.5 mg/dL) within 24 hours of rasburicase administration. RESULTS: Fifty-five patients were recruited for this study. Pediatric patients (< 18 years) accounted for 43.6% of cases. Rasburicase was provided prophylactically to 43 patients (78.2%) and for treating TLS to 12 (21.8%). Mean ± standard deviation serum uric acid at baseline and 24 hours was 9.2 ± 1.8 mg/dL and 3.2 ± 2.1 mg/dL, respectively. There was significant reduction in the serum uric acid and creatinine (P < .001) within 24 hours of rasburicase administration. The response was maintained up to 72 hours. A single dose of rasburicase was effective in 94.5% of patients. Single low-dose rasburicase led to 95% direct cost savings compared to the recommended dose. CONCLUSION: Single-dose rasburicase with frequent laboratory monitoring is effective in the management of TLS and offers significant cost reductions.

A Real-World Evaluation of the Long-Term Safety and Efficacy of Infliximab in the Treatment Moderate-to-Severe Psoriasis.

INTRODUCTION: Psoriasis is a chronic immune-mediated inflammatory skin disease that occurs in 2.5-3.5% of the general population. Infliximab (INF), a TNF-α inhibitor biologic agent, is a long-standing efficacious treatment for psoriasis; however, not all patients sustain a long-term response (LTR) because of a number of factors including antibody production. There is a paucity of studies assessing infliximab efficacy over a period ≥ 5 years. METHODS: A retrospective cohort chart review of our clinic patients who had undergone ≥ 5 years of treatment with infliximab for chronic plaque psoriasis was performed. The following variables were recorded and analyzed with the Fisher exact test: age, sex, body mass index ([BMI]; normal weight [NW], overweight [OW], obese [OB]), changes in infliximab strength (dose or frequency), concomitant systemic therapy, and side effects. Clinical improvement was assessed by comparing the total body surface area (tBSA) affected by psoriasis before and after treatment. RESULTS: There was a significant difference in likelihood of achieving LTR between the NW, OW and OB groups (p = 0.044). Non-normal-weight patients (OW + OB) were significantly more likely to achieve and sustain LTR than NW patients (OR 9.07, p = 0.020). There were no other significant associations for the other evaluated variables. LIMITATIONS: Patients who began treatment with infliximab before 2009 (prior to the use of the clinic's electronic medical record) were excluded. The Psoriasis Area and Severity Index (PASI) was not available for this study. CONCLUSION: Surprisingly, patients who are overweight or obese are more likely to obtain long-term clinical benefit in their psoriasis symptoms with infliximab therapy than patients who are normal weight.

Assessment of anti-factor Xa activity of enoxaparin for venous thromboembolism prophylaxis in morbidly obese surgical patients.

BACKGROUND: Venous thromboembolism (VTE) can be encountered by 60% of hospitalized patients. Anticoagulants have been recommended to reduce the risk of VTE in patients with risk factors. However, no specific dosing recommendations for obese patients are provided in the current practice guidelines. The purpose of this study was to determine the efficacy and safety of weight-based dosing of enoxaparin for VTE prophylaxis among morbidly obese patients undergoing surgery. METHODS: Adult patients were enrolled if they have a body mass index (BMI) of ≥35 kg/m2 and were scheduled for surgery. These patients were prescribed enoxaparin (0.5 mg/kg subcutaneously [SC] once daily). Peak anti-factor Xa levels were measured 4 h after the third dose of enoxaparin. The primary outcome measure was to determine whether a weight-based dosing of enoxaparin of 0.5 mg/kg produce the anticipated peak anti-Xa levels (0.2-0.6 IU/m) among obese patients undergoing surgery. Secondary outcomes include the incidence of VTE, the incidence of minor or major bleeding, and the incidence of heparin-induced thrombocytopenia (HIT). RESULTS: Fifty patients were enrolled in the study. The mean age was 53 ± 16 years, 74% of the patients were female. The mean BMI was 40.5 ± 5, and the average enoxaparin dose was 50 ± 9.8 SC daily. Nearly 88% of the patients reached the target anti-factor Xa (0.427 ± 0.17). None of the patients developed HIT or VTE. There was no incidence of major or minor bleeding. CONCLUSIONS: Weight-based enoxaparin dose led to the anticipated peak anti-Xa levels (0.2-0.6 IU/mL) in most of the morbidly obese study patients undergoing surgery without any evidence of major side effects. The weight-based dosing of enoxaparin was also effective in preventing VTE in all patients. Although these results are promising, further comparative trials are needed in the setting of morbidly obese surgical patients.