Intravenous Infusion Of Midazolam Research Articles

Convulsioni e gastroenterite: un caso che insegna

The article reports a case of convulsions with gastroenteritis (CWG) and briefly reviews the related literature. A 2-year-old girl presented with four short episodes of focal afebrile seizures within 12 hours. She had fever with vomiting in the previous 2 days and she developed diarrhoea during her hospital stay, after the fifth seizure. She had no significant past medical history and showed neither neurological signs nor signs of dehydration. Serum electrolytes were normal, cerebrospinal fluid examination was negative for meningoencephalitis and contrast-enhanced CT Brain scan showed no evidence of intracranial lesion. Stool investigation was positive for rotavirus. Therefore, the diagnosis of CWG was made. Repeated convulsions were handled with continuous intravenous infusion of midazolam. The main cause of CWGs in viral gastroenteritis is due to rotavirus or norovirus. The convulsions are usually focal seizure clusters, with secondary generalization. CWGs are associated with a benign prognosis.

Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial.

Adolescent depression is prevalent and is associated with significant morbidity and mortality. Although intravenous ketamine has shown efficacy in adult treatment-resistant depression, its efficacy in pediatric populations is unknown. The authors conducted an active-placebo-controlled study of ketamine's safety and efficacy in adolescents. In this proof-of-concept randomized, double-blind, single-dose crossover clinical trial, 17 adolescents (ages 13-17) with a diagnosis of major depressive disorder received a single intravenous infusion of either ketamine (0.5 mg/kg over 40 minutes) or midazolam (0.045 mg/kg over 40 minutes), and the alternate compound 2 weeks later. All participants had previously tried at least one antidepressant medication and met the severity criterion of a score >40 on the Children's Depression Rating Scale-Revised. The primary outcome measure was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 hours after treatment. A single ketamine infusion significantly reduced depressive symptoms 24 hours after infusion compared with midazolam (MADRS score: midazolam, mean=24.13, SD=12.08, 95% CI=18.21, 30.04; ketamine, mean=15.44, SD=10.07, 95% CI=10.51, 20.37; mean difference=-8.69, SD=15.08, 95% CI=-16.72, -0.65, df=15; effect size=0.78). In secondary analyses, the treatment gains associated with ketamine appeared to remain 14 days after treatment, the latest time point assessed, as measured by the MADRS (but not as measured by the Children's Depression Rating Scale-Revised). A significantly greater proportion of participants experienced a response to ketamine during the first 3 days following infusion as compared with midazolam (76% and 35%, respectively). Ketamine was associated with transient, self-limited dissociative symptoms that affected participant blinding, but there were no serious adverse events. In this first randomized placebo-controlled clinical trial of intravenous ketamine in adolescents with depression, the findings suggest that it is well tolerated acutely and has significant short-term (2-week) efficacy in reducing depressive symptoms compared with an active placebo.Reprinted from Am J Psychiatry 2021; 178:352-362 with permission from American Psychiatric Association Publishing.

Inter-hospital transfer of a pregnant prone patient with COVID-19 as a bridge to ECMO.

Sir, Pregnant women are at a higher risk of severe coronavirus disease 2019 (COVID-19) compared to non-pregnant women and are associated with worse outcomes.[1] The management of acute respiratory distress syndrome (ARDS) in a pregnant woman is challenging because of physiological changes of pregnancy and the detrimental effects of hypoxaemia and hypercarbia on the foetus. Prone ventilation and extracorporeal membrane oxygenation (ECMO) are effective rescue strategies in severe ARDS requiring invasive mechanical ventilation. We transferred a pregnant patient with critical COVID-19 on invasive mechanical ventilation (IMV) and prone position as a bridge to ECMO. A 28-year-old primigravida at 24 weeks’ gestation, with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was admitted for breathing difficulty and cough since 8 days. She was started on oxygen by face mask to target oxygen saturation (Spo2) ≥94%, dexamethasone 6 mg intravenous once daily and enoxaparin 40 mg subcutaneous 12 hourly. Laboratory parameters showed C-reactive protein 140 mg/L, haemoglobin 12.8 gm%, white cell count 4200/mm3, procalcitonin 1.1 ng/ml, lactate dehydrogenase 680 U/L, D-dimer 1011 ng/ml and normal renal and liver function tests. Her oxygenation worsened the next day, and a trial of continuous positive airway pressure (CPAP) was given in the intensive care unit (ICU). However, because of worsening oxygenation and respiratory distress, the patient was tracheal-intubated and started on IMV with lung-protective ventilation strategy. The patient remained hypoxaemic (partial pressure of oxygen to a fraction of inspired oxygen (PaO2/FiO2) ratio of 67 mm Hg) and higher plateau pressure (Pplat) of 32 cm H2O. She was proned with shoulder and thigh support and adequate padding of pressure areas. The abdomen and pelvis were kept in a suspended position. Periodical foetal assessment was performed using cardiotocography and portable Doppler ultrasound, while the suspended abdomen was checked manually for any obstruction or tension. The patient continued to be severely hypoxaemic (PaO2/FiO2 <80 mm Hg) despite two sessions of prone ventilation of 16 h each. The case was discussed with the ECMO team at Central Command Centre as a potential candidate for ECMO. Given the absence of retrieval ECMO and level III neonatal ICU, an inter-hospital transfer was planned. Due to rapid desaturation on supine positioning, a decision to transfer the patient in prone position was taken. A team of two anaesthesiologist-intensivists and three ICU trained nurses accompanied the patient. Heart rate, rhythm, arterial blood pressure, end-tidal continuous waveform capnography, SpO2 and ventilator waveforms were monitored continuously throughout the patient care [Table 1]. The tracheal tube was firmly secured with a tube holder and standard tie. An intravenous infusion of propofol and midazolam was used for sedation, and cisatracurium was used for neuromuscular blockade. The patient was transferred as a single unit with shoulder and pelvic support from the ICU bed to the ambulance stretcher. One staff was solely dedicated for foetal assessment and airway. An intensivist was responsible for IMV, and another supervised the transfer. The transfer was uneventful with continuous monitoring of the patient and foetus. The ECMO facility was approximately 9 km away and took a travel time of 28 min.Table 1: Vitals of the patient during inter-hospital transportProne ventilation is an effective rescue strategy for the management of refractory hypoxaemia in severe ARDS by improving ventilation-perfusion matching and reducing mortality.[2] Pregnancy is traditionally excluded from trials on ARDS. However, protocolised proning with due consideration to physiological changes of pregnancy and adequate monitoring is recommended as a low-cost and effective strategy in ARDS management.[3] The transfer in the prone position can be catastrophic with a risk of the misplaced airway and rapid deoxygenation or inability to perform cardiopulmonary resuscitation during an emergency.[4] The systematic planning of transfer with attention to airway, monitoring and pressure areas was found to have been successful in a smaller case series.[56] The twin issues of second-trimester pregnancy and prone position made this case challenging. However, adequate planning, team briefing and continuous patient and foetal monitoring ensured a safe transfer. In conclusion, safe transfer of a pregnant, prone patient was possible with adequate planning, risk management and an experienced team. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Status Dystonicus in Children: A Cross-Sectional Study and Review of Literature.

Background: Status dystonicus is a life-threatening, underrecognized movement disorder emergency. We aimed to ascertain the etiology, clinical presentation, complications, and outcomes of status dystonicus in children and reviewed the literature for similar studies. Methods: Records of all children aged <14 years admitted to a single center with status dystonicus between 2014 and 2018 were reviewed. Results: Twenty-four children (75% male) were identified with status dystonicus. The annual incidence rate was 0.05 per 1000 new admissions <12 years of age. The mean age at presentation was 6.3 ± 3.6 years. Median duration of hospital stay was 10.5 days (interquartile range 5-21.7). The severity of dystonia at presentation was grade 3 (n = 9; 37.5%) and 4 (n = 9; 37.5%). The most common triggering factor was intercurrent illness/infection (n = 18; 75%). The most common underlying etiologies were cerebral palsy (n = 8; 33.3%), complicated tubercular meningitis (n = 3; 12.5%), and mitochondrial disorders (n = 3; 12.5%). Basal ganglia involvement was seen in 15 cases (62.5%). Respiratory and/or bulbar compromise (n = 20; 83.3%) and rhabdomyolysis (n = 15; 62.5%) were most commonly seen. Oral trihexyphenidyl (96%) followed by oral or intravenous diazepam (71%), oral baclofen (67%), and midazolam infusion (54%) were the most common drugs used. Clonidine was used in 33% cases, without any significant side effects. Three children died owing to refractory status dystonicus and its complications; the mortality rate was 12.5%. Conclusion Status dystonicus is a neurologic emergency in children with severe dystonia, with significant complications and a high mortality rate. Static and acquired disorders are more common than heredo-familial causes. Identification and treatment of infection in children is important as the majority of cases are triggered by an intercurrent infection.

Comparison of the effect of continuous intravenous infusion of sodium valproate and midazolam on management of status epilepticus in children

Background and ObjectivesStatus epilepticus as a pediatric emergency requires rapid seizure control in order to prevent subsequent disabilities. Therefore, the present study was conducted to compare the efficacy and side effects of continuous intravenous infusion of sodium valproate versus midazolam as a third-line treatment of status epilepticus in children. MethodologyThis randomized clinical trial study included all children with convulsive and non-convulsive status epilepticus admitted to the pediatric intensive care unit (PICU) of the Bu-Ali Sina Hospital in Sari City (Mazandaran Province, Iran) who had not responded to first-line treatment with diazepam and second-line treatment with phenytoin or phenobarbital. They were consequently treated with continuous intravenous infusion of sodium valproate or midazolam to control persistent seizures. ResultsThe study comprised 70 patients who were randomly assigned to two equal groups of sodium valproate or midazolam treatment. The mean age of patients in group A (sodium valproate) and group B (midazolam) was 3.97 ± 3.33 and 3.84 ± 2.93 years, respectively. In the present study, the most common etiology of status epilepticus was remote symptomatic, accounting for 35% of cases in the two groups. Sodium valproate was effective in controlling status epilepticus in 91.4% of patients, while midazolam was found to be effective in 85.7% of patients (p > 0.05). Patients who received sodium valproate had shorter seizure duration after administration of the drug compared to those who received midazolam (p = 0.01). Eight patients in the midazolam group and two patients in the sodium valproate group were intubated (p = 0.023). The mean duration of stay in the PICU was 3.2 ± 1.4 and 5.6 ± 2.8 days in groups A and B, respectively, showing a significant difference (p = 0.001). ConclusionAccording to our findings, intravenous infusion of sodium valproate can be used as an effective and relatively safe treatment in children with all types of status epilepticus, especially in challenging situations such as lack of intensive care units or respiratory problems.

Super-refractory status epilepticus and pharmacoresistant epilepsy in an infant with hemorrhagic shock and encephalopathy syndrome

Introduction. Hemorrhagic shock and encephalopathy syndrome (HSES) is a rare disorder with prevalence at an early age. The main features of HSES are acute diarrhea, shock, disseminated intravascular coagulation, multisystem impairment, and encephalopathy. The prognosis is very poor, with high mortality, especially in cases with status epilepticus. Case outline. The presented infant had typical features of HSES associated with super-refractory status epilepticus as de novo epileptic event, followed by pharmacoresistant epilepsy. Clinical course of the disease was very severe and required urgent circulatory and respiratory support, and simultaneous management of super-refractory status epilepticus by continuous intravenous infusion of midazolam, barbiturate, and levetiracetam. The outcome was very poor with serious neurological consequence and resistant epileptic seizures. Conclusion. The treatment of the presented patient with HSES was very challenging due to a lifethreatening condition associated with super-refractory status epilepticus, and further pharmacoresistant epilepsy. Additionally, the choice of antiepileptic drugs is limited due to multisystem impairment and adverse effects which might worsen the already severe course of the disease.

Reversal of Ketamine Induced Acute Delirium with Continuous Midazolam Infusion in a Post Extubation Child with Refractory Bronchospasm: A Case Report

Continuous ketamine infusion has been used successfully to treat severe refractory bronchospasm in children requiring mechanical ventilation in the intensive care setting. One of the common side effects known is emergence delirium. There is no standardized treatment for the ketamine-induced emergence delirium although benzodiazepine, haloperidol and dexmedetomidine have been reported to be effective in the past. A 7-year-old girl admitted to a tertiary hospital for life-threatening asthma requiring immediate intubation and ventilation. Ketamine was used as sedative and bronchodilator in anticipation of her challenging ventilation strategy. She was successfully extubated on day 8 of admission, however, she developed symptoms associated with the delirium. Successful reversal of the symptoms was achieved after 48-hour use of low dose intravenous midazolam. This was the first case reported on the reversal of ketamine-induced emergence phenomenon using low dose intravenous midazolam infusion.

Pilot randomized active-placebo-controlled trial of low-dose ketamine for the treatment of multiple sclerosis–related fatigue

Background: Fatigue is the most common symptom of MS and has no effective pharmacotherapy. Objective: To determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue. Methods: In this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and reported fatigue received a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). The primary outcome was change in Daily Fatigue Severity (DFS) for 7 days following the infusion. Secondary outcomes included Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) measured up to day 28 post-infusion. We analyzed changes in all outcomes using mixed-effect models. Results: In total, 18 participants were enrolled; 67% participants received ketamine. Side effects of ketamine were transient. No change in the DFS was observed after 7 days (−0.10 point; 95% confidence interval (CI): −0.32, 0.12; p = 0.40). We observed a trend in reduced FSS scores at 1 week (−5.2 points; 95% CI: −10.4, 0.14; p = 0.06) and a clinically and statistically significant reduction in MFIS score at day 28 (−13.5 point; 95% CI: −25.0, −1.98; p = 0.04). Conclusions: Ketamine infusions were safe and well-tolerated. While no change in DFS after 7 days was observed, secondary analyses suggest a benefit of ketamine infusion for reduction of longer term fatigue severity in people with MS.

The Oral Bioavailability and Metabolism of Midazolam in Stable Critically Ill Children: A Pharmacokinetic Microtracing Study.

Midazolam is metabolized by the developmentally regulated intestinal and hepatic drug‐metabolizing enzyme cytochrome P450 (CYP) 3A4/5. It is frequently administered orally to children, yet knowledge is lacking on the oral bioavailability in term neonates up until 1 year of age. Furthermore, the dispositions of the major metabolites 1‐OH‐midazolam (OHM) and 1‐OH‐midazolam‐glucuronide (OHMG) after oral administration are largely unknown for the entire pediatric age span. We aimed to fill these knowledge gaps with a pediatric [14C]midazolam microtracer population pharmacokinetic study. Forty‐six stable, critically ill children (median age 9.8 (range 0.3–276.4) weeks) received a single oral [14C]midazolam microtracer (58 (40–67) Bq/kg) when they received a therapeutic continuous intravenous midazolam infusion and had an arterial line in place enabling blood sampling. For midazolam, in a one‐compartment model, bodyweight was a significant predictor for clearance (0.98 L/hour) and volume of distribution (8.7 L) (values for a typical individual of 5 kg). The typical oral bioavailability in the population was 66% (range 25–85%). The exposures of OHM and OHMG were highest for the youngest age groups and significantly decreased with postnatal age. The oral bioavailability of midazolam, largely reflective of intestinal and hepatic CYP3A activity, was on average lower than the reported 49–92% for preterm neonates, and higher than the reported 21% for children> 1 year of age and 30% for adults. As midazolam oral bioavailability varied widely, systemic exposure of other CYP3A–substrate drugs after oral dosing in this population may also be unpredictable, with risk of therapy failure or toxicity.

Difference in imaging biomarkers between transient and permanent neurological deficits after endovascular treatment of cerebrovascular aneurysms.

The literature suggests that blood-brain barrier disruption (BBBD) plays a significant role in the development of neurological events in patients with diffusion-weighted imaging (DWI) that is negative for lesions. In this prospective, single-center cohort study, the authors compared the imaging characteristics of patients suffering transient neurological events (TNEs) with those in patients suffering permanent neurological events (PNEs) after having undergone elective embolization of unruptured intracranial aneurysms. This prospective cohort study was conducted between July 2016 and June 2019. Inclusion criteria were adults undergoing elective neuroendovascular procedures and the absence of contraindications to MRI. All subjects underwent brain MRI including postcontrast FLAIR (pcFLAIR) sequences for evaluation of BBBD within 24 hours postprocedure. In total, 128 patients harboring 133 unruptured aneurysms were enrolled, 109 of whom (85.2%) showed some degree of BBBD on pcFLAIR MRI and 50 of whom (39.1%) suffered an ischemic insult per DWI. In total, 23 patients (18%) suffered neurological complications, 16 of which (12.5%) were TNEs and 7 of which (5.5%) were PNEs. The median extent of BBBD was focal in asymptomatic patients as compared to hemispheric and lobar in the TNE and PNE groups, respectively (p < 0.001). The American Society of Anesthesiologists physical status classification predicted the extent of BBBD (p = 0.046). Lesions on DWI were noted in 34 asymptomatic patients (32.4%) compared to 9 patients (56.3%) with TNEs and all 7 patients (100%) with PNEs (p < 0.001). The median number of DWI lesions was 0 (range 0-18 lesions) in the asymptomatic group compared to 1.5 (range 0-8 lesions) and 8 (range 1-13 lesions) in the TNE and PNE groups, respectively (p < 0.001). Smoking (p = 0.008), older age (p = 0.002), and longer surgery (p = 0.006) were positively associated with the number of lesions on DWI. On multivariate analysis, intraarterial verapamil (p = 0.02, OR 8.01, 95% CI 1.35-47.43) and extent of BBBD (p < 0.001, OR 58.58, 95% CI 9.48-361.84) were positively associated with the development of TNEs, while intravenous infusion of midazolam during surgery (p = 0.02, OR 6.03, 95% CI 1.29-28.20) was negatively associated. An increased number of lesions on DWI was the only significant predictor for the development of PNEs (p < 0.001, OR 49.85, 95% CI 5.56-447.10). An increasing extent of BBBD was associated with the development of TNEs, whereas an increasing number of lesions on DWI was significantly associated with the development of PNEs. BBBD imaging using pcFLAIR may serve as a valuable biomarker for detecting subtle cerebral ischemia and stratifying the risk for ischemic events.

Continuous intravenous versus intermittent bolus midazolam with remifentanil during arteriovenous fistula placement with monitored anesthesia care in chronic renal failure patients: a randomized controlled trial.

ABSTRACTBACKGROUND: There is limited data on the use of intravenous continuous infusion (CI) versus intravenous intermittent bolus (IB) doses of midazolam for conscious sedation in patients with chronic renal failure. Unexpected adverse events can occur in chronic renal failure patients undergoing short procedures.OBJECTIVE: Investigate and compare the sedoanalgesic and adverse effects of intravenous continuous infusion (CI) use of midazolam with intravenous intermittent bolus (IB) doses of midazolam while using intravenous remifentanil as a rescue medication, and assess patient and surgeon satisfaction.DESIGN: Prospective, randomized, single-blind controlled study.SETTINGS: Two tertiary care hospitals.PATIENTS AND METHODS: Study included patients aged 43-81 years with a diagnosis of chronic renal failure who were referred for an arteriovenous fistula procedure with modified anesthesia care between August 2012 and April 2016. The patients were randomized to intravenous CI or IB doses of midazolam. IB doses of remifentanil were used as a rescue medication.MAIN OUTCOME MEASURES: Primary outcomes were amounts of midazolam and remifentanil medications during the operation, the amount of remifentanil as a rescue medication, and the satisfaction of patient and surgeon.SAMPLE SIZE: 116 assessed for eligibility; 99 randomized to CI (n=50) or IB doses (n=49 of midazolam).RESULTS: The total dose of midazolam by CI was greater than with midazolam by IB (P=.002). The total dose of remifentanil was higher with IB doses of midazolam in comparison to CI of midazolam (P=.001). The groups were similar in sedation and pain control, duration of procedure, recovery time, patient satisfaction and adverse events; surgeon satisfaction was greater with CI versus IB (P=.035).CONCLUSION: Intravenous CI midazolam during MAC provides better surgeon satisfaction then IB midazolam and can be used safely for arteriovenous fistula procedures.LIMITATIONS: Two different surgeon groups.CONFLICT OF INTEREST: None.

The effect of dexmedetomidine and midazolam on combined spinal-epidural anesthesia in patients undergoing total knee arthroplasty.

BackgroundIntravenous dexmedetomidine has been reported to potentiate the anesthetic effect of local anesthetics and improve the quality of postoperative analgesia when used as an adjuvant in neuraxial block. We compared the effects of intravenous dexmedetomidine and midazolam for sedation on combined spinal-epidural (CSE) anesthesia.MethodsThis study included 50 patients undergoing total knee arthroplasty. CSE anesthesia was given using 10 mg bupivacaine for all patients. After checking the maximum sensory and motor levels, the patients were randomly allocated into two groups of 25 each to receive intravenous continuous infusion of dexmedetomidine (Group D) or midazolam (Group M) for sedation during surgery. Regression block level, hemodynamic changes, and sedation score were compared between the groups when the patients entered the postanesthetic care unit (PACU). For patient-controlled epidural analgesia, 0.2% levobupivacaine with 650 µg of fentanyl (150 ml in total) was infused at a rate of 1 ml/h, in addition to a 3-ml bolus dose with a 30-min lockout time. The visual analogue scale scores, additional analgesic demand, patient satisfaction, and adverse events between the two groups were also compared postoperatively.ResultsA significant difference was observed in relation to the sensory block level in the PACU (Group D: 6.3 ± 2.1; Group M: 3.2 ± 1.9) (P = 0.002). The motor block level and other outcomes showed no significant intergroup differences.ConclusionsIntravenous injection of dexmedetomidine, rather than midazolam, for procedural sedation is associated with prolonged sensory block, with comparable incidences of adverse events during CSE anesthesia.

Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis

PurposeThe aim of the present study was to develop a population pharmacokinetic model of midazolam, and to evaluate the influence of maturation process and other variability factors in critically ill children with severe acute bronchiolitis, who received a long-term intravenous infusion of midazolam. MethodsIn the study were included 49 critically ill children of both genders (from 0 to 130 weeks of age) with severe acute bronchiolitis hospitalised in intensive care units. Nonlinear mixed effects modelling approach was applied for data analyses and simulations. ResultsThe final model is a two-compartment model that includes the effects of body weight using allometric scaling with fixed exponents and maturation of clearance. For a typical subject, scaled to the adult body weight of 70 kg, population pharmacokinetic values were estimated at 8.52 L/h for clearance (when maturation function was 1), 25.5 L/h for intercompartmental clearance, and 5.71 L and 39.8 L for the volume of the central and peripheral compartment, respectively. Based on the final model, maturation reaches 50% of the adult clearance in 45.9 weeks of postmenstrual age. The influence of gender, ABCB1 genotype and biochemical parameters on midazolam clearance was not detected. Results of simulations indicate the need for reduced dosing in certain groups of patients in order to maintain plasma concentrations of midazolam within recommended values. ConclusionsThe developed population pharmacokinetic model can contribute to the dosing optimisation of midazolam, especially in critically ill children as it includes the influence of size and maturation of clearance, which are important parameters for achieving the desired plasma concentrations of midazolam.

A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial

Research has suggested that subanesthetic doses of ketamine may work to improve cocaine-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of this trial was to test whether a single ketamine infusion improved treatment outcomes in cocaine-dependent adults engaged in mindfulness-based relapse prevention. Fifty-five cocaine-dependent individuals were randomly assigned to receive a 40-minute intravenous infusion of ketamine (0.5 mg/kg) or midazolam (the control condition) during a 5-day inpatient stay, during which they also initiated a 5-week course of mindfulness-based relapse prevention. Cocaine use was assessed through self-report and urine toxicology. The primary outcomes were end-of-study abstinence and time to relapse (defined as first use or dropout). Overall, 48.2% of individuals in the ketamine group maintained abstinence over the last 2 weeks of the trial, compared with 10.7% in the midazolam group (intent-to-treat analysis). The ketamine group was 53% less likely (hazard ratio=0.47; 95% CI=0.24, 0.92) to relapse (dropout or use cocaine) compared with the midazolam group, and craving scores were 58.1% lower in the ketamine group throughout the trial (95% CI=18.6, 78.6); both differences were statistically significant. Infusions were well tolerated, and no participants were removed from the study as a result of adverse events. A single ketamine infusion improved a range of important treatment outcomes in cocaine-dependent adults engaged in mindfulness-based behavioral modification, including promoting abstinence, diminishing craving, and reducing risk of relapse. Further research is needed to replicate these promising results in a larger sample.

Midazolam\u2013ketamine versus dexmedetomidine\u2013ketamine combinations for anesthesia of pediatric patients undergoing cardiac catheterization

BackgroundThe aim of the current study was to compare the effects of midazolam–ketamine versus dexmedetomidine–ketamine combinations on hemodynamics, sedation level, and recovery period in pediatric patients undergoing cardiac catheterization for hemodynamic study.Patients and methodsFifty pediatric patients undergoing cardiac catheterization for hemodynamic study were enrolled in the current study. Patients were randomly distributed to one of two equal groups: midazolam–ketamine group (group M) and dexmedetomidine–ketamine group (group D). The patients in group M received intravenous midazolam 0.1 mg/kg and ketamine 1 mg/kg as a bolus for induction, then received an intravenous midazolam infusion of 0.1 mg/kg/h and ketamine infusion of 1 mg/kg/h for maintenance whereas patients in group D received intravenous dexmedetomidine1μg/kg and ketamine 1 mg/kg as a bolus for induction, then received an intravenous dexmedetomidine infusion of 0.5 μg/kg/h and ketamine infusion of 1 mg/kg/h for maintenance. Mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (SPO2), and sedation scores were recorded. Recovery time, perioperative adverse events, and total ketamine consumption required for anesthesia maintenance were also recorded.ResultsThe HR was significantly lower in group D when compared with group M at 10, 20, and 30 min of the procedure with no significant difference as regards the MAP between the two study groups. There were no statistically significant differences between the two study groups in terms of Ramsay sedation scores. Ketamine consumption in group D was significantly lower than in group M. The recovery time was significantly shorter in group D when compared with group M.ConclusionThe dexmedetomidine–ketamine combination was superior to midazolam–ketamine combination because of less intraoperative ketamine consumption required for adequate intraoperative sedation and the shorter recovery time.

Liver transplantation for acute liver failure due to hepatitis E in a pregnant patient.

Liver transplantation for acute liver failure due to hepatitis E in a pregnant patient.

Seizure management in children requiring palliative care: a review of current practice.

Controlling seizures in children approaching death can be difficult, and there is a limited evidence base to guide best practice. We compared current practice against the guidance for seizure management produced by the Association of Paediatric Palliative Medicine (APPM). Retrospective case note review of episodes of challenging seizure management in children receiving end-of-life care over a 10-year period (2006-2015) in the south-west region of England. We reviewed 19 admissions, in 18 individuals. Six (33%) had a malignancy, nine (50%) had a progressive neurodegenerative condition and three (17%) had a static neurological condition with associated epilepsy. Thirteen (72%) died in their local hospice, four (22%) at home, and one (6%) in hospital. Seventeen of 19 episodes involved the use of subcutaneous or intravenous midazolam infusion, for a mean of 11 days (range 3-27). There was a wide range of starting doses of midazolam, and 9/17 (53%) received final doses in excess of current dose recommendations. Six individuals received subcutaneous phenobarbital infusions, with four of these (67%) receiving final doses in excess of current dose recommendations. Plans for adjustments of infusion rates, maximal doses or alternative approaches should treatment fail were inconsistent or absent. In 16/18 (88%) cases seizures were successfully controlled prior to the day of the child's death. Staff found the experience of managing seizures at end of life challenging and stressful. Pharmacological approaches to seizure management in end-of-life care are variable, often exceeding APPM dose recommendations. Despite this, safe and effective seizure control was possible in all settings.

Sedation during spinal anaesthesia : A comparison between Dexmedetomidine and midazolam infusion.

Objective: To study the effects of intravenous dexmedetomidine infusion and compare it with intravenous midazolam infusion during spinal anaesthesia (S/A) with regards to effect on psychomotor performance, memory and any side effect. Materials Methods: A prospective randomized double blind study was conducted on 60 patients of ASA I to III, scheduled for lower abdominal or lower limb surgery under S/A. All patients were randomly divided into two groups of 30 each; randomization was done by computer generated random numbers. In Group D, dexmedetomidine 1 μg/kg and In Group M, midazolam 0.04 mg/kg basal infusion for 10 min then S/A was given with hyperbaric bupivacaine (0.5%). After achieving required level of S/A; position given and then infusion of inj. Dexmedetomidine 0.5µg/kg/hr in group D and Inj. Midazolam 0.04mg/kg/hr by infusion started. Both psychomotor and memory test were performed before study drug infusion and after 1 and 4 hour of stoppage of infusion. Results: Thus, in both the groups, psychomotor performance was not significantly changed as compared to baseline at 1 hour and 4 hour after stoppage of infusion. There was significantly decreased in recall of picture, after 1 hour of study drug infusion in both the groups (anterograde amnesia); which was regained at 1 hour after stoppage of infusion. The mean time required to achieved sedation score (RSS) of 3 were statistically significant shorter in group D as compared to in group M (P 0.05). Conclusion: Thus, we conclude that, Dexmedetomidine provide rapid onset of arousable sedation without causing respiratory and cardiovascular depression. It provides anterograde amnesia with rapid recovery of psychomotor function.

Does evidence from randomized controlled trials support the use of intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit?

Does evidence from randomized controlled trials support the use of intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit?

Ketamine Infusion as a Counter Measure for Opioid Tolerance in Mechanically Ventilated Children: A Pilot Study.

Drug rotation to prevent opioid tolerance is well recognized in chronic pain management. However, ketamine infusion as a counter measure for opioid tolerance is rarely described in mechanically ventilated children developing tolerance from prolonged opioid infusion. We performed a retrospective study in a 14-bed medical-surgical-cardiac pediatric intensive care unit. Thirty-two mechanically ventilated children who had developed tolerance from prolonged intravenous infusion of opioids received a continuous intravenous infusion of ketamine as an opioid substitute for more than 2days, scheduled in a drug rotation protocol. Thirty-two children (median age 2.5years, range 0.1-16.0; weight 11.2kg [3.8-62.0]) were included. Patients had received continuous intravenous infusion of opioids and benzodiazepines for 16.0days (4.0-34.0) when drug rotation was started. The median dose of continuous intravenous infusion of ketamine was 4.0mg·kg-1·h-1 (1.8-6.0) and the median duration was 3.0days (2.0-6.0). After having restarted opioids, fentanyl doses were significantly lower compared with the time before the drug rotation began (after, 2.9µg·kg-1·h-1 [0.8-4.9] vs before, 4.15µg·kg-1·h-1 [1.2-10.0]; p<0.001). Continuous intravenous infusion of midazolam and clonidine were unchanged during drug rotation. COMFORT-B scoring was significantly lower after having started drug rotation (after, 14.5 [8-19] vs before, 16 [11-22]; p<0.001). Drug rotation with ketamine in mechanically ventilated children with opioid tolerance is feasible and seems to reduce the rate of fentanyl infusion.