Continuous Infusion Research Articles

Blinatumomab infusion interruptions in pediatric patients rarely lead to readmission.

Blinatumomab is a bispecific T-cell engager administered as a 28-day continuous infusion. Infusions can be associated with interruptions requiring support from clinical staff, but the frequency of interventions with outpatient blinatumomab has not been characterized. This study is a single-center, retrospective review of patients who received blinatumomab between December 3, 2014 and October 31, 2021 to determine frequency and type of interventions. Forty patients received blinatumomab for 69 cycles. Clinical staff intervention was required in 31 (45%) cycles, only six (8.7%) cycles needed readmission. Management of outpatient blinatumomab infusions requires education and training of clinical staff and caregivers to quickly troubleshoot interruptions.

Pediatric Lead Chelation Managed During Critical Medication Shortages: Case Report and Literature Review.

Lead poisoning in children has the potential for devastating neurodevelopmental consequences. There is significant socioeconomic disparity in children with lead poisoning. Specific lead chelation regimens have been approved for children by the US Food and Drug Administration, however in the United States, there has been a recent national shortage of the primary therapy, edetate calcium disodium (CaNa2 EDTA). This case report presents a 23-month-old child with severe symptomatic lead poisoning during a national shortage of CaNa2 EDTA to highlight the need for advocacy regarding critical medication shortages, especially for antidote therapy. The infant's initial blood lead level was 364 mcg/dL and he received a continuous infusion of CaNa2 EDTA (1000 mg/m2/day), as well as dimercaprol (4 mg/kg intramuscularly every 4 hours). The supply of CaNa2 EDTA was exhausted on day 3 of therapy so he was transitioned to enteral succimer monotherapy. Initial parenteral therapy of 72 hours achieved a lead level of 72 mcg/dL; he then completed his enteral course of succimer along with environmental mitigation. However, elevated blood lead levels persisted and he subsequently required 3 more courses of enteral succimer, and he continues to have detectable blood lead levels 2 years after initial presentation. In the face of medication shortages including CaNa2 EDTA, and now also dimercaprol, clinicians must create and study alternative chelation therapy regimens for pediatric lead toxicity. Furthermore, public policy initiatives, including the development of a national supply stockpile of chelation agents, must be created in order to minimize supply chain disruption and ensure adequate and equitable antidote therapy for lead poisoning outbreaks.

Opioid free versus opioid sparing strategies for multimodal antinociception during laparoscopic colectomy: a randomised controlled trial

BackgroundIt remains unclear whether opioid-free anesthesia (OFA), when compared to opioid-sparing anesthesia (OSA), reduces postoperative opioid consumption while still providing adequate pain control. We thus tested the hypothesis that patients having an OFA strategy during laparoscopic colectomy would require less postoperative opioids when compared to an OSA strategy. MethodsThis single-center, prospective randomized controlled superiority trial, randomly allocated consecutive patients undergoing laparoscopic colectomy to receive either sevoflurane-dexmedetomidine anesthesia with a continuous infusion of lidocaine and ketamine (OFA group) or sevoflurane-sufentanil boluses anesthesia with a continuous infusion of lidocaine (OSA group). Both groups received multimodal antinociception with boluses of dexamethasone, lidocaine, and ketamine during anesthesia induction, as well as acetaminophen, ketoprofen, and nefopam before the end of the surgery. OFA patients also received a dose of magnesium sulfate during induction. The primary outcome was cumulative opioid consumption at 48 h after surgery, expressed in oral morphine equivalents (OME). Secondary exploratory outcomes were pain scores, opioid-related adverse events, and patient quality of life (WHODAS score). ResultsOf the 160 randomized patients, 155 were included in a modified intention-to-treat analysis. Median [Q1-Q3] OME consumption at 48 hours after surgery did not differ between groups (9 [0-30] mg for OFAvs. 14 [0-30] mg for OSA; p = 0.861). Key secondary outcomes were not different between groups except a three time higher incidence of bradycardia in the OFA group. ConclusionsIn patients undergoing laparoscopic colectomy with a multimodal antinociception protocol, OFA, when compared to OSA, did not decrease postoperative opioid consumption. Clinical Trial Registry and NumberNCT05031234.

Renal Function and Its Impact on the Concentration of Ceftazidime-Avibactam: A cross-sectional study

ObjectivesThis study measured the effect of renal function on the plasma concentrations of ceftazidime and avibactam in critically ill patients. We also sought to measure the concentration ratio of ceftazidime to avibactam. MethodsThis was a cohort study at a tertiary referral centre in Italy, on patients treated with continuous infusion of ceftazidime-avibactam (CAZ-AVI) between November 2019 and December 2023. The association between creatine clearance (CrCl) and free plasma ceftazidime and avibactam concentration, as well as CAZ-AVI ratio was explored to assess correlation and potential risk to fail to achieve target therapeutic concentration. Results52 patients, predominantly male (75%), with a median age of 68.5 years were included. Our analyses provided strong evidence for inverse correlation between CrCl and both free-CAZ (r=-0.627; R2=0.3936; P<0.001) and free-AVI plasma concentration (r=-0.619; R2=0.3832; P<0.001). Overall CrCl alone could explain about 40% of overall variation of either free-CAZ and free-AVI. Linear models suggest that free-CAZ and free-AVI concentration drop of about 7.31% and 9.23% for each 10 point increase of CrCl, respectively. . Assessment of the CAZ-AVI ratio supports a direct linear association with CrCl suggesting that free-AVI concetration is more affected by CrCl variation than free-CAZ concentration. Patients with CrCl ≥130 mL/min showed a significantly higher risk of suboptimal drug exposure (i.e. less than 4 times the MIC) both to CAZ and AVI. ConclusionThe findings emphasize the need for individualized dosing strategies of CAZ-AVI based on renal function, for antibiotics used in critically ill patients. The study suggests that underdosing in patients with high CrCl is likely to be common and as such could affect drug effectiveness.

Sleep Health Composite and Diabetes Symptom Burden in Young Adults With Type 1 Diabetes.

Multiple individual sleep health dimensions (satisfaction, regularity, and duration) are associated with diabetes symptoms, precursors to micro-and macrovascular complications, among young adults with type 1 diabetes mellitus (T1DM). Nearly half of young adults with T1DM develop vascular complications; however, modifiable contributors of diabetes symptoms, including sleep health, have been understudied. This cross-sectional quantitative descriptive study involved the completion of multiple validated self-report questionnaires and the collection of raw continuous glucose monitor and diary data over a 14-day period. The sleep health composite score was calculated by summing the number of dimensions with "good" sleep health. Chronotype was estimated with the 19-item Morningness-Eveningness Questionnaire. Multiple linear regression analyses were conducted to evaluate the associations between the independent variables (sleep health composite and chronotype) and diabetes symptom burden. Covariates, including age, race, sex at birth, T1D duration, continuous subcutaneous insulin infusion use, and hemoglobin A1C (HbA1C), were considered to determine their contribution to these relationships. One hundred nineteen young adults with T1DM who were aged 18 to 26 years were included in this study from 2 cohorts. Higher sleep health composite scores were associated with a lower overall diabetes symptom burden, even after adjusting for covariates in the linear regression models. Initially, a later chronotype was linked to a higher diabetes symptom burden, but this association became insignificant after accounting for HbA1C levels. Improving multiple dimensions of sleep health may alleviate the diabetes symptom burden among young adults with T1DM.

Association of single bolus versus bolus followed by infusion of tranexamic acid with blood loss in adolescent idiopathic scoliosis surgery

BackgroundAdolescent idiopathic scoliosis (AIS) corrective surgery may involve significant blood loss and blood transfusion requirements. Antifibrinolytic agents such as tranexamic acid (TXA) have been used to reduce blood loss, but its optimal dose is uncertain. The objective of this study is to determine the estimated blood loss and rate of blood transfusion between two groups of AIS patients receiving TXA as a single bolus versus bolus followed by infusion in scoliosis surgery.MethodsThis was a retrospective analysis of a single bolus versus bolus followed by infusion of TXA in AIS surgery. AIS patients undergoing posterior spinal fusion (PSF) from December 2018 to September 2019 at a tertiary university hospital were identified. Inclusion criteria were patients aged between 10 and 21 years who received either a single bolus of 30 mg/kg TXA (Group A) or a single bolus of 30 mg/kg followed by continuous infusion of 10 mg/kg/h of TXA (Group B). Patient demographics, operative data, estimated blood loss, blood transfusion rate, and complications were recorded.ResultsA total of 129 AIS patients were included. All operative surgeries were performed by two senior consultants. The mean age was 14.8 ± 3.4 years old, and 89.1% were female. The Cobb angle, number of fusion levels, number of screws, length of skin incision, and duration of surgery were comparable between the two groups. There was no difference in the total estimated blood loss between the two groups: 723.3 ± 279.4 mL (range: 175.0–1607.0 mL) in Group A and 819.4 ± 302.6 mL (range: 330.0–1556.0 mL) in Group B (p = 0.065). There were no complications, and none received blood transfusion.ConclusionTXA when administered as a single bolus or bolus followed by infusion in AIS patients undergoing PSF surgery was associated with similar estimated total surgical blood loss and blood transfusion requirement.

Target Attainment and Population Pharmacokinetics of Cefazolin in Patients with Invasive Staphylococcus aureus Infections: A Prospective Cohort Study.

This study aimed to determine cefazolin target attainment in patients with invasive Staphylococcus aureus (S. aureus) infections and to develop a population pharmacokinetic (PK) model. Adult patients with invasive S. aureus infections treated with cefazolin bolus infusions were included. Unbound and total trough and mid-dose cefazolin concentrations were measured, and strain-specific MICs were determined. The primary outcome was the proportion of patients attaining 100% fT>MIC at all time points evaluated. A population PK model was developed, using non-linear mixed-effects modelling. Overall, 51 patients were included, with a total of 226 unbound and total cefazolin concentrations measured (mean: 4.4 per patient). The median daily dosage in patients with an estimated glomerular filtration rate of >60 mL/min/m2 was 8 g. The median age was 74 years (interquartile range (IQR) 57-82) and 26% were female. A history of chronic kidney disease and acute kidney injury were present in 10/51 (19.6%) and 6/51 (11.7%), respectively. Achievement of 100% fT>MIC occurred in 86% of the patients and decreased to 45% when a target of 100% fT>4xMIC was evaluated. The mean unbound cefazolin fraction was 27.0% (standard deviation (SD) 13.4). Measured and estimated mean cefazolin trough concentrations differed significantly [13.1 mg/L (SD 23.5) vs. 7.4 mg/L (SD 7.9), p < 0.001]. In the population PK model, elevated estimated creatinine clearance and bolus instead of continuous application were covariates for target non-attainment. In conclusion, cefazolin target achievement was high, and the measurement of the unbound cefazolin concentration may be favored. The Monte Carlo simulations indicated that target attainment was significantly improved with continuous infusion.

Efficacy of methylene blue in refractory septic shock: study protocol for a multicenter, randomized, placebo-controlled trial

BackgroundSeptic shock is now the leading cause of mortality in intensive care units (ICUs). Refractory septic shock requires high doses of vasopressors. Some previous studies have revealed that methylene blue could improve hypotension status and help reduce the dosage of catecholamines. This study aims to investigate the clinical effect of methylene blue in septic shock and explore whether it can increase arterial pressure and reduce the usage of vasopressors.MethodsThis study is a multicenter, randomized, placebo-controlled trial planning to include 100 refractory septic shock patients. The protocol is to administer a bolus of 2 mg/kg methylene blue intravenously followed by a continuous infusion of 0.5 mg/kg/h for 48 h. The primary outcome is the total dose of vasopressor required in refractory septic shock in the first 48 h. Secondary outcomes include other hemodynamic parameters, oxygen metabolism indexes, tissue perfusion indexes, major organ function indexes, and certain plasma cytokines and other factors.DiscussionThis protocol aims to evaluate the safety and efficacy of methylene blue as adjuvant therapy for refractory septic shock. The main outcome measure will be vasopressor requirements and hemodynamic parameters. Additionally, bedside ultrasonography, blood gases, and cytokines will be assessed to evaluate perfusion, respiratory, and metabolic effects. The results are intended to provide evidence on the safety and efficacy of methylene blue in refractory septic shock, guiding clinical decision-making.Trial registrationThis clinical trial has been registered at ChiCTR (https://www.chictr.org.cn/) on March 16, 2023. ChiCTR registration number: ChiCTR2300069430.

Does insulin pump therapy offer benefits for behaviour, mood, cognition and HbA1c in children and adolescents with type 1 diabetes? A randomised controlled trial with observational follow-up

AimsImproved behaviour, mood, cognition and HbA1c have been reported with short-term use of continuous subcutaneous insulin infusion (CSII) in youth with type 1 diabetes (T1D). We sought to re-examine these...

Continuous Catheter Techniques Versus Single-Injection Nerve Blocks: A Comprehensive Review of Postoperative Pain Management Strategies.

Effective postoperative pain management is crucial for optimizing patient recovery and enhancing surgical outcomes. This review compares two prominent regional anesthesia techniques, continuous catheter techniques and single-injection nerve blocks, focusing on their efficacy, safety, and impact on patient outcomes. Single-injection nerve blocks involve administering a one-time anesthetic dose to a specific nerve or plexus, offering immediate but transient pain relief. In contrast, continuous catheter techniques utilize a catheter to deliver a continuous infusion of anesthetic, providing extended analgesia. The review synthesizes current evidence on the effectiveness of each method, highlighting that single-injection blocks are advantageous for their simplicity and rapid onset but may require supplementary pain management for longer procedures. Continuous catheter techniques, while offering prolonged pain relief, carry risks such as infection and catheter displacement. The comparative analysis of these techniques reveals that both have distinct roles in postoperative care, with choice depending on the surgical procedure and patient needs. Patient satisfaction, recovery times, and overall outcomes are critical factors in determining the optimal pain management strategy. Future research should focus on refining these techniques and exploring innovations to improve patient care and pain management outcomes. This review provides insights for clinicians to make informed decisions about postoperative pain management to enhance patient comfort and recovery.

Continuous infusion of beta-lactam antibiotics in critically ill patients with sepsis: implementation considerations

Continuous infusion of beta-lactam antibiotics in critically ill patients with sepsis: implementation considerations

Body composition in a pediatric population with type-1 diabetes – The importance of planned physical exercise

Objective and methodsThis study aimed to assess the body composition of pediatric patients with type-1 diabetes (T1D) in a Portuguese pediatric endocrinology/diabetic clinic, using the InBody 570 bioimpedance system. Preschool children (<6 years) and those recently diagnosed (<6 months) were excluded. ResultsThe study included 78 patients (53% female). Median age at assessment was 14 years, with 81% pubertal children. Eighty-seven percent were using continuous subcutaneous insulin infusion (CSII), 25% with an automated closed-loop model. Median HbA1c was 7.3%. Most had an adequate body mass index (BMI) standard deviation score (62%) and 48% engaged in regular physical exercise (PE) outside of school. Median percentage body fat (PBF) was 21.5% and was abnormal in 48%, with median visceral adiposity of 4. Despite adequate BMI, 11% had excessive PBF. PBF was significantly associated with visceral fat (r=0.79; P<0.001), female gender (P<0.001) and PE performed out of school (P=0.005). PE was associated with lower PBF (P=0.005), lower visceral fat (P=0.002), and higher muscle-to-fat ratio (P=0.006). ConclusionEngaging in physical exercise out of school correlated significantly with improved body composition, characterized by reduced PBF and diminished visceral adiposity. Considering the known benefits of physical exercise for metabolic and glycemic control, this study highlights the importance of promoting regular physical exercise in T1D patients.

Parenteral nutrition results in peripheral ileal to hepatic circadian discordance in mice

Background: We have developed a mouse model of Parenteral Nutrition Associated Liver Disease in which PN infusion results in cholestatic liver injury. In the liver, the master circadian genes Arntl/Bmal drive rhythmic gene expression and regulate circadian expression of hepatic functions including bile acid synthesis. The aim of this study was to examine the effect of continuous PN on ileal and hepatic expression of circadian regulatory (CR) genes, FXR signaling and bile acid synthesis in mice. Methods: WT mice were exposed to continuous soy oil lipid emulsion-based PN infusion through a central venous catheter for 4 days (PN). Water was provided ad libitum, but no nutrients were provided enterally. On d4, mice were sacrificed every 6 hours (7AM, 1PM, 7PM and 1AM), and ileal, hepatic tissue and serum harvested. From tissue samples, the relative expression of circadian transcription factors and FXR signaling was assessed. Results: Administration of 4d PN increased hepatic injury, inflammatory cytokine expression and gut permeability. In the ileum, PN activated FXR and induced expression of Fgf15 and Nr0b2. In the liver, expression of FXR-downstream targets was dysregulated. PN administrations impacted hepatic and ileal circadian transcription factor mRNA expression which was discordant between the two organs. Conclusions: Dysregulation of circadian regulatory machinery is in part due to discordance of the gut-liver axis during PN. Pharmacologic targeting of CR as a therapeutic strategy for PNALD thus deserves further investigation.

Automating insulin delivery through pump and continuous glucose monitoring connectivity: Maximizing opportunities to improve outcomes.

The development of automated insulin delivery (AID) systems, which connect continuous glucose monitoring (CGM) systems with algorithmic insulin delivery from an insulin pump (continuous subcutaneous insulin infusion, [CSII]), has led to improved glycaemia and quality of life benefits in those with insulin-treated diabetes. This review summarizes the benefits gained by the connectivity between insulin pumps and CGM devices. It details the technical requirements and advances that have enabled this, and highlights the clinical and user benefits of such systems. Clinical trials and real-world outcomes from the use of AID systems in people with type 1 diabetes (T1D)will be the focus of this article; outcomes in people with type 2 diabetes (T2D) and other diabetes subtypes will also be discussed. We also detail the limitations of current technological approaches for connectivity between insulin pumps and CGM devices. While recognizing the barriers, we discuss opportunities for the future.

Development and Validation of a High-Performance Liquid Chromatography-Ultraviolet Spectrometry Method for Ampicillin and its Application in Routine Therapeutic Drug Monitoring of Intensive Care Patients.

Ampicillin/sulbactam, a combination of a β-lactam and β-lactamase inhibitor, is widely used in clinical settings. However, therapeutic drug monitoring (TDM) of ampicillin is not commonly performed, particularly in intensive care units (ICUs). The purpose of this study was to develop and validate a rapid and cost-effective high-performance liquid chromatography (HPLC)-ultraviolet spectrometry method to quantify ampicillin in human serum and evaluate its clinical application in ICU patients. Sample cleanup included a protein precipitation protocol, followed by chromatographic separation on a C18 reverse-phase HPLC column within 12.5 minutes using gradient elution of the mobile phase. The assay was validated according to the German Society of Toxicology and Forensic Chemistry criteria. Clinical applications involved the retrospective analysis of TDM data from ICU patients receiving continuous infusion of ampicillin/sulbactam, including the attainment of target ranges and individual predicted and observed pharmacokinetics. The method was robust, with linear relations between the peak area responses and drug concentrations in the range of 2-128 mg/L. The coefficient of variation for precision and the bias for accuracy (both interday and intraday) were less than 10%. Clinical application revealed variable pharmacokinetics of ampicillin in ICU patients (clearance of 0.5-31.2 L/h). TDM-guided dose adjustments achieved good therapeutic drug exposure, with 92.9% of the samples being within the optimal (16-32 mg/L) or quasioptimal (8-48 mg/L) range. This method provides a practical solution for the routine TDM of ampicillin, facilitating individualized dosing strategies to ensure adequate therapeutic drug exposure. Given its simplicity, cost-effectiveness, and clinical relevance, HPLC-ultraviolet spectrometry holds promise for broad implementation in hospital pharmacies and clinical laboratories.

Continuous infusion of resolvin D2 in combination with Angiotensin-II show contrary effects on blood pressure and intracardiac artery remodeling

Specialized pro-resolving mediators (SPMs) are key effectors of resolution of inflammation. This is highly relevant for cardiac and vessel remodeling, where the net inflammatory response contributes to determine disease outcome. Herein, we used a mice model of angiotensin (Ang)–II–induced hypertension to study the effect of the SPM Resolvin D2 (RvD2), on hypertension and cardiac remodeling. By using subcutaneous osmotic minipumps, mice were treated with PBS or Ang-II in combination with or without RvD2 for two weeks. Mice receiving RvD2 gained less blood pressure increase compared to Ang-II alone. Surprisingly, however, examination of intracardiac arteries revealed that RvD2 treatment in combination with Ang-II exacerbated Ang–II–induced fibrosis. Measures of vascular smooth muscle cell dedifferentiation correlated with the level of vascular remodeling, indicating that this dedifferentiation, including increased proliferation and migration, is a contributing factor. RNA sequencing of left ventricle cardiac tissue supported these findings as pathways related to cell proliferation and cell differentiation were upregulated in mice treated with Ang-II in combination with RvD2. Additionally, the RNA sequencing also showed upregulation of pathways related to SPM metabolism. In line with this, Mass spectrometry analysis of lipid mediators showed reduced cardiac levels of the arachidonic acid derived metabolite leukotriene E4 in RvD2 treated mice. Our study suggests that continuous infusion through osmotic minipumps should not be the recommended route of RvD2 administration in future studies.

Comparison of thoracic epidural catheter and continuous peripheral infusion for management of traumatic rib fracture pain.

Thoracic epidural catheters (TECs) are useful adjuncts to multimodal pain regimens in traumatic rib fractures. However, TEC placement is limited by contraindications, patient risk profile, and provider availability. Continuous peripheral infusion of ketamine and/or lidocaine is an alternative that has a modest risk profile and few contraindications. We hypothesized that patients with multiple traumatic rib fractures receiving TECs would have better pain control, in terms of daily morphine milligram equivalents (MMEs) and mean pain scores (MPSs) when compared with continuous peripheral infusions of ketamine and/or lidocaine. We retrospectively analyzed traumatic rib fracture admissions to a level 1 trauma center between January 2018 and December 2020. We evaluated two treatment groups: TEC only and continuous infusion only (drip only). A linear mixed-effects model evaluated the association of MME with treatment group. An interaction term of treatment group by time (days 1-7) was included to allow estimating potential time-dependent treatment effect on MME. A zero-inflated Poisson mixed-effects model evaluated the association of treatment with MPS. Both models adjusted for confounders. A total of 1,647 patients were included. After multivariable analysis, a significant, time-varying dose-response relationship between treatment group and MME was found, indicating an opioid-sparing effect favoring the TEC-only group. The opioid-sparing benefit for TEC-only therapy was most prominent at day 3 (27.4 vs 36.5 MME) and day 4 (27.3 vs 36.2 MME) (p < 0.01). The drip-only group had 1.21 times greater MPS than patients with TEC only (p < 0.001). Drip-only analgesia is associated with higher daily MME use and MPS, compared with TEC only. The maximal benefit of TEC therapy appears to be on days 3 and 4. Prospective, randomized comparison between groups is necessary to evaluate the magnitude of the treatment effect. Therapeutic/Care Management; Level III.

Glycemic and Psychosocial Outcomes of Advanced Hybrid Closed Loop Therapy in Youth With High HbA1c: A Randomized Clinical Trial.

To determine the efficacy of advanced hybrid closed loop (AHCL) therapy in a high-risk cohort of youth on continuous subcutaneous insulin infusion (CSII) ± continuous glucose monitoring (CGM) with suboptimal glycemia. In a 6-month multicenter clinical trial, youth with type 1 diabetes with mean and most recent HbA1c > 8.5% (65 mmol/mol) were randomly assigned 1:1 to AHCL or treatment as usual (CSII ± CGM). The primary outcome was the 24-week between-group difference in HbA1c. Secondary outcomes included CGM metrics from masked CGM and psychological measures (youth-reported problem areas in diabetes [PAID], quality of life, anxiety, depression, and hypoglycemia fear) assessed using validated questionnaires. A total of 42 participants were randomized (mean [SD] age 16.2 [2.5] years, HbA1c 9.8 [1.1]% or 84 [12] mmol/mol, PAID score 50.3 [19.8]). At study end, the mean (SD) HbA1c was 8.8 (1.1)% or 73 (12) mmol/mol with AHCL and 9.9 (1.2)% or 85 (13.1) mmol/mol with CSII ± CGM, with mean adjusted group difference of -0.77% (95% CI -1.45 to -0.09) or -8.4 mmol/mol (-15.8 to -1.0); P = 0.027. AHCL increased time in range 70-180 mg/dL (difference 19.1%; 95% CI 11.1 to 27.1), reduced time >180 mg/dL (difference -17.7%; 95% CI -26.6 to -8.8), with no increase in time spent <70 mg/dL (difference -0.8%; 95% CI -2.7 to 0.6). There was no evidence for difference in psychosocial outcomes between the two groups at study end. AHCL should be encouraged in youth with suboptimal glycemia, as AHCL improves glycemia. However, psychological support remains vital, as technology alone may not be able to reduce the burden of diabetes care in this subgroup.

Extravasation with methylthioninium chloride

Introduction Methylthioninium chloride is used for multiple treatment purposes and is sometimes administered through peripheral intravenous lines. We highlight the potential adverse effects of methylthioninium chloride extravasation during continuous peripheral intravenous administration. Case summary A 38-year-old woman presented to the emergency department with multifactorial hypovolemic and septic shock. She was treated with a continuous peripheral infusion of intravenous methylthioninium chloride for shock refractory to multiple vasopressors. Images One day after administration commenced, the patient developed blue staining of the left upper arm due to extravasation of methylthioninium chloride proximal to the site of infusion. Further images show its later spread. Conclusion While reported cases of methylthioninium chloride extravasation are rare, it is our preference that methylthioninium chloride should be administered through a central line in cases of continuous infusion due to the risk of potential toxicity from extravasation.

L-carnitine for valproic acid-induced toxicity.

Review the effectiveness and dosing of L-carnitine for valproic-acid induced toxicity. A literature review of the pharmacokinetics and clinical use of L-carnitine was performed. Valproic acid is a fatty acid used for numerous therapeutic indications ranging from epilepsy to bipolar disorder. The metabolism of valproic acid produces both therapeutic and toxic metabolites. Whilst it has a good safety profile, adverse effects of valproic acid in chronic use include hepatotoxicity ranging from transient elevation of liver enzymes to fulminant liver failure and hyperammonaemia with resultant encephalopathy. L-carnitine is an essential cofactor for mitochondrial fatty acid metabolism, which is an important source of energy in cardiac and skeletal muscle. Physiological concentrations of L-carnitine are maintained in man by exogenous dietary intake and endogenous synthesis. Following exogenous oral administration of L-carnitine, the bioavailability ranges from 14% to 18%. After bolus intravenous administration of L-carnitine in doses ranging from 20 to 100 mg/kg, the volume of distribution is 0.2-0.3 L/kg, and the fraction excreted unchanged in urine is 0.73-0.95, suggesting that renal clearance of L-carnitine is dose dependent due to saturable renal reabsorption at supraphysiological concentrations. There is evidence supporting the use of L-carnitine in treating hyperammonaemia and hepatotoxicity following chronic therapeutic use and after acute overdose of valproic acid, but the optimal dose and route of administration is unknown. Based on the pharmacokinetics of L-carnitine, we advocate the administration of L-carnitine for valproic-acid induced hyperammonaemia or hepatotoxicity as an intravenous loading dose of 5 mg/kg followed by a continuous intravenous infusion instead of the oral or intravenous boluses that are currently advocated.