Midazolam Infusion Research Articles

Dexmedetomidine combined with midazolam infusion guided by bispectral index during bronchoscopy.

Conscious sedation guided by bispectral index (BIS) during bronchoscopy has been proved to be a feasible approach. This study aimed to investigate the safety and efficacy of dexmedetomidine combined with midazolam for undergoing conscious sedation during bronchoscopy. The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry. Patients were randomized into DEX group (dexmedetomidine combined with midazolam) and FEN group (fentanyl combined with midazolam). Bronchoscopy was performed under awake sedation titrated to a BIS level of 60-80. The primary endpoint was the incidence of hypoxia, the secondary endpoint was the incidence of bradycardia and hypotension, effect of sedation including satisfaction degree (VAS) of the operators and patients and patients' willingness to undergo bronchoscopy again. A total of 222 cases in DEX group and 211 cases in FEN group completed the study. The incidence of hypoxia and tachycardia in DEX group was lower than that in FEN group (8.1% vs 14.7%, 10.4% vs 19.0%, p<0.05), and the incidence of hypotension and bradycardia in DEX group was higher than that in FEN group (6.8% vs 0, 15.3% vs 8.1%, p<0.05). Midazolam dosage was significantly lower in the DEX group than in the FEN group, and the duration of surgery was significantly longer in the DEX group. The differences in intraoperative discomfort of VAS score, satisfaction VAS score, and willingness rate to undergo bronchoscopy again were not statistically significant between the two groups. In addition, the proportion of "procedural interference by patient movement" in DEX group was higher than that in FEN group. The conscious sedation regimen of dexmedetomidine combined with midazolam monitored by BIS is considered to be safe and effective during bronchoscopy. The occurrence of hypoxia and tachycardia was less, and the fluctuation of blood pressure and heart rate was mild, but the proportion of bradycardia in dexmedetomidine group was higher than that in fentanyl combined with midazolam group.

Age-Specific Dose Regimens of Dexmedetomidine for Pediatric Patients in Intensive Care Following Elective Surgery: A Phase 3, Multicenter, Open-Label Clinical Trial in Japan.

To demonstrate the efficacy, safety, and pharmacokinetics of dexmedetomidine as a potential sedative for pediatric surgery patients in the ICU. Phase 3, multicenter, open-label study. This study included 61 patients at 13 tertiary hospitals in Japan. Pediatric patients (≥ 45 wk corrected gestational age to < 17 yr) undergoing intensive care treatment with mechanical ventilation requiring greater than 6 hours estimated duration of sedation following elective cardiac surgery. Dexmedetomidine was IV administered without a loading dose at age-specific dose regimens 0.2-1.4 (< 6 yr) and 0.2-1.0 µg/kg/hr (≥ 6 yr). The primary endpoint was the percentage of patients who did not require a rescue sedative (midazolam) infusion during mechanical ventilation or for the first 24 hours of a greater than 24 hours ventilation following the commencement of dexmedetomidine administration. Overall, 47 of the 61 patients (77.0%) did not require rescue midazolam. Adverse events were reported in 53 patients (86.9%). Frequently observed adverse events were hypotension (47.5%), bradycardia (31.1%), and respiratory depression (26.2%). Most of these adverse events were mild, a few moderate, and none severe. Although serious adverse events occurred in four patients, including one cardiac tamponade resulting in the withdrawal of dexmedetomidine, none of the adverse events resulted in mortality or were directly related to dexmedetomidine. The plasma dexmedetomidine concentration generally reached the target concentration of 0.3-1.25 ng/mL at 1-2 hours prior to completion of administration or immediately prior to the commencement of tapering. The age-specific dose regimens of dexmedetomidine without an initial loading dose achieved an adequate sedation level during mechanical ventilation and caused no clinically significant adverse events in the intensive care pediatric patients. These effects were achieved within the therapeutic range of dexmedetomidine plasma concentration and were accompanied by minimal effects on hemodynamics and respiration.

TO COMPARE THE INTUBATING CONDITIONS WITH DEXMEDETOMIDINE VERSUS MIDAZOLAM-FENTANYL COMBINATION FOR AWAKE FIBREOPTIC INTUBATION

Objectives:To compare the intubating conditions of dexmedetomidine alone versus fentanyl -midazolam combination during AFOI Methodology: Group-I patients (n=30) received dexmedetomidine 1µg/kg bolus infusion over 10 minutes, followed by infusion of 0.1 µg/kg/hr titrated to 0.7 µg/kg/hr whereas Group-II patients (n=30) received i.v fentanyl 2µg/kg bolus followed by midazolam infusion of 0.02-0.1mg/kg/hr until they were adequately sedated i.e. Ramsay Sedation Score (RSS) of 3 .Intraoperatively Total Comfort Score, 5 point FOI score was noted and Questionnaire assessment was done 24 hours after surgery. Results: During preoxygenation, the mean TCS was not statistically signicant different between the two groups but during FOS and during intubation, the mean TCS was lower in group-1than group-2and the difference between the two groups was statistically signicant.(p&lt;0.05). Signicant differences in the patient's reaction to tube were found during FOS and after intubation between the two groups with lower reaction in dexmedetomidine group(p≤0.05). During follow-up assessment 24 hours after the surgical procedure, the dexmedetomidine group patients judged their sedation more positively and were having less pain and discomfort during the procedure than fentanyl plus midazolam patients. Conclusion: The use of dexmedetomidine at 1mcg/kg bolus over 10 minutes, with maintenance rates of 0.1-0.7 μg/kg/hr offer better tolerance, preservation of a patent airway and spontaneous ventilation, while maintaining hemodynamic stability during AFOI.

Influence of alphaxalone on motor somatosensory evoked potentials in a female rhesus macaque (Macaca mulatta).

This communication reports the effect of alphaxalone on motor somatosensory evoked potential (SEPs) in a rhesus macaque. The animal was deeply anaesthetised with an infusion of ketamine, medetomidine, midazolam and alfentanil. The median nerve was stimulated, and SEPs were recorded from the motor cortex. The successive administration of three doses of alphaxalone (0.5, 1 and 2 mg/kg) induced an increase of the latency time and a decrease of the amplitude of the SEPs. However, the structure of the waveforms was conserved, and hence alphaxalone might represent a suitable general anaesthetic option in neuroscience research as well as veterinary or human medicine.

A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors' previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD. Individuals with chronic PTSD (N=30) were randomly assigned (1:1) to receive six infusions of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) (psychoactive placebo control) over 2 consecutive weeks. Clinician-rated and self-report assessments were administered 24 hours after the first infusion and at weekly visits. The primary outcome measure was change in PTSD symptom severity, as assessed with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), from baseline to 2 weeks (after completion of all infusions). Secondary outcome measures included the Impact of Event Scale-Revised, the Montgomery-Åsberg Depression Rating Scale (MADRS), and side effect measures. The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2. At week 2, the mean CAPS-5 total score was 11.88 points (SE=3.96) lower in the ketamine group than in the midazolam group (d=1.13, 95% CI=0.36, 1.91). Sixty-seven percent of participants in the ketamine group were treatment responders, compared with 20% in the midazolam group. Among ketamine responders, the median time to loss of response was 27.5 days following the 2-week course of infusions. Ketamine infusions were well tolerated overall, without serious adverse events. This randomized controlled trial provides the first evidence of efficacy of repeated ketamine infusions in reducing symptom severity in individuals with chronic PTSD. Further studies are warranted to understand ketamine's full potential as a treatment for chronic PTSD.

A comparative randomized clinical trial to assess the efficacy between dexmedetomidine and midazolam infusions for procedural sedation during septoplasty

Background: Septoplasty is often performed under sedation with local anesthesia. Midazolam is one of the commonly used sedative but it lacks analgesic effect. Dexmedetomidine is now preferred, owing to the side effects of midazolam. However, there seems to be addressable literature void in this regard. This study was aimed to evaluate and compare the effectiveness of sedation between midazolam and dexmedetomidine infusions for procedural sedation during septoplasty under local anesthesia Patients and Methods: This was a randomized clinical trial involving sixty patients undertaking elective septoplasty under local anesthesia randomized into Group A that received intravenous dexmedetomidine 1 μg/kg over 10 min, followed by continuous infusion 0.5 μg/kg/h and Group B receiving intravenous midazolam 50 μg/kg (over 10 min), followed by continuous infusion 50 μg/kg/h. The Ramsay sedation score (RSS) and patient and surgeon satisfaction scores were documented. The analysis was done using the Chi-square test and Student t-test. Results: A significant change in the heart rate from 10 to 60 min was observed between the two groups (P < 0.05). The midazolam group showed a significant increase in mean arterial pressure (MAP) from baseline to 40 min time interval (P < 0.05). The respiratory rate remained constant in both groups. Patients attaining target RSS of 3–4 were significantly higher in the dexmedetomidine group (P < 0.05). Patient satisfaction score and surgeon satisfaction score were higher in the dexmedetomidine group (P < 0.05). Conclusion: Dexmedetomidine for septoplasty under local anesthesia is more effective than midazolam infusion in providing adequate sedation and provides stable hemodynamics and well-preserved respiratory functions.

A Comparative Randomized Clinical Trial to Assess the Efficacy between Dexmedetomidine and Midazolam Infusions for Procedural Sedation during Septoplasty

Abstract Background: Septoplasty is often performed under sedation with local anesthesia. Midazolam is one of the commonly used sedative but it lacks analgesic effect. Dexmedetomidine is now preferred, owing to the side effects of midazolam. However, there seems to be addressable literature void in this regard. This study was aimed to evaluate and compare the effectiveness of sedation between midazolam and dexmedetomidine infusions for procedural sedation during septoplasty under local anesthesia Patients and Methods: This was a randomized clinical trial involving sixty patients undertaking elective septoplasty under local anesthesia randomized into Group A that received intravenous dexmedetomidine 1 μg/kg over 10 min, followed by continuous infusion 0.5 μg/kg/h and Group B receiving intravenous midazolam 50 μg/kg (over 10 min), followed by continuous infusion 50 μg/kg/h. The Ramsay sedation score (RSS) and patient and surgeon satisfaction scores were documented. The analysis was done using the Chi-square test and Student t-test. Results: A significant change in the heart rate from 10 to 60 min was observed between the two groups (P &lt; 0.05). The midazolam group showed a significant increase in mean arterial pressure (MAP) from baseline to 40 min time interval (P &lt; 0.05). The respiratory rate remained constant in both groups. Patients attaining target RSS of 3–4 were significantly higher in the dexmedetomidine group (P &lt; 0.05). Patient satisfaction score and surgeon satisfaction score were higher in the dexmedetomidine group (P &lt; 0.05). Conclusion: Dexmedetomidine for septoplasty under local anesthesia is more effective than midazolam infusion in providing adequate sedation and provides stable hemodynamics and well-preserved respiratory functions.

Continuous midazolam infusion can minimize the pro-inflammatory response to anesthesia and surgery for pediatric patients with intra-abdominal infection: Comparative study versus continuous propofol infusion

ABSTRACT Objectives : Comparison of serum levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) estimated before and after propofol or midazolam infusion during emergency surgery for children had intraabdominal infection (IAI) Patients & Methods : 140 children were allocated into Group P: included patients received propofol at the rate of 11 mg/kg/hr and Group M included patients received midazolam infusion at the rate of 0.3 mg/kg/hr. Anesthesia was induced with intravenous (IV) thiopentone (5 mg/kg) and maintained with 50% air in oxygen and an end-tidal concentration of 2–3% sevoflurane with IV rocuronium (0.6 mg/kg) and IV injection of paracetamol (10 mg/kg) as intraoperative analgesia. Study infusions were started before skin incision and stopped after skin closure. Blood samples were obtained before the start and at end of infusion for ELISA estimation of serum IL-1β, IL-6 and TNF-α levels. Study outcome is the effect of the study drugs on estimated serum cytokines’ levels. Results At the end of propofol infusion, serum cytokines’ levels were significantly higher in comparison to levels estimated before start of infusion. while, at the end of midazolam infusion, serum cytokines’ levels were significantly decreased in comparison to levels estimated before the start of infusion. Conclusion Midazolam infusion not propofol infusion decreased serum cytokines’ levels and could modulate the preexisting proinflammatory status of pediatric patients with IAI and prevent the immune stress of anesthesia and surgery.

Association of Continuous Opioids and/or Midazolam During Early Mechanical Ventilation with Survival and Sensorimotor Outcomes at Age 2 Years in Premature Infants: Results from the French Prospective National EPIPAGE 2 Cohort

To evaluate the association of early continuous infusions of opioids and/or midazolam with survival and sensorimotor outcomes at age 2years in very premature infants who were ventilated. This national observational study included premature infants born before 32weeks of gestation intubated within 1hour after birth and still intubated at 24hours from the French EPIPAGE 2 cohort. Infants only treated with bolus were excluded. Treated infants received continuous opioid and/or midazolam infusion started before 7days of life and before the first extubation. Naive infants did not receive these treatments before the first extubation, or received them after the first week of life, or never received them. This study compared treated (n=450) vs naive (n=472) infants by using inverse probability of treatment weighting after multiple imputation in chained equations. The primary outcomes were survival and survival without moderate or severe neuromotor or sensory impairment at age2 years. Survival at age 2 years was significantly higher in the treated group (92.5% vs 87.9%, risk difference, 4.7%; 95% CI, 0.3-9.1; P=.037), but treated and naive infants did not significantly differ for survival without moderate or severe neuromotor or sensory impairment (86.6% vs 81.3%; risk difference, 5.3%; 95% CI -0.3 to 11.0; P=.063). These results were confirmed by sensitivity analyses using 5 alternative models. Continuous opioid and/or midazolam infusions in very premature infants during initial mechanical ventilation that continued past 24hours of life were associated with improved survival without any difference in moderate or severe sensorimotor impairments at age 2years.

Effects of PEEP on Hemodynamic Variables of Pigs Submitted to Volume-controlled Ventilation under Pneumoperitoneum associated to Cephalodeclive

Background: Videolaparoscopic procedures have gained prominence due to their low invasiveness, causing less surgical trauma and better post-surgical recovery. However, the increase in intra-abdominal pressure due to the institution of pneumoperitoneum can alter the patient's homeostasis. Therefore, volume-controlled ventilation, associated with positive end-expiratory pressure (PEEP), improves arterial oxygenation and prevents pulmonary collapse, but it can lead to important hemodynamic changes. The aim of this study was to evaluate, comparatively, the effects of positive end expiratory-pressure (PEEP) on hemodynamic variables of pigs submitted to volume-controlled ventilation, during pneumoperitoneum and maintained in head-down tilt and determine which PEEP value promotes greater stability on hemodynamic variables. Materials, Methods &amp; Results: Twenty-four pigs were used, between 55 and 65-day-old, weighing between 15 and 25 kg, randomly divided into 3 distinct groups differentiated by positive end-expiratory pressure: PEEP 0 (volume-controlled ventilation and PEEP of 0 cmH2O), PEEP 5 (volume-controlled ventilation and PEEP of 5 cmH2O) and PEEP 10 (volume-controlled ventilation and PEEP of 10 cmH2O). Volume-controlled ventilation was adjusted to 8 mL/kg of tidal volume and a respiratory rate of 25 movements per min. Anesthesia was maintained with continuous infusion of propofol (0.2 mg/kg/min) and midazolam (1 mg/kg/h). Pneumoperitoneum was performed with carbon dioxide (CO2), keeping the intra-abdominal pressure at 15 mmHg and the animals were positioned on a 30° head-down tilt. The evaluations of hemodynamic variables started 30 min after induction of anesthesia (M0), followed by measurements at 15-min intervals (from M15 to M90), completing a total of 7 evaluations. The variables of interest were collected over 90 min and submitted to analysis of variance followed by Tukey´s post-hoc test, with P &lt; 0.05. The PEEP 10 group had higher values of CVP and mCPP, while the PEEP 5 group, mPAP and PVR were higher. The PEEP 0 group, on the other hand, had higher means of CI. Regarding the moments, there were differences in HR, SAP, DAP, MAP, CO, IC and TPR.Discussion: According to the literature, important hemodynamic effects due to pneumoperitoneum are reported, which can be caused by the pressure used in abdominal insufflation, CO2 accumulation, duration of the surgical procedure, hydration status and patient positioning. Mechanical ventilation associated with PEEP can also cause an increase in intrathoracic pressure and, therefore, reduce cardiac output. Cardiovascular changes are proportional to the PEEP used. Central venous pressure (PVC) measure the patient's preload, and intrathoracic pressure can interfere with this parameter. The peak pressure values in the PEEP 10 group were higher than the other groups, demonstrating that the increase in intrathoracic pressure results in higher PVC values. Regarding PAPm and PCPm, these variables can be influenced according to the PEEP values and the patient's position. In relation to CI, the increase in PEEP may reflect on intrathoracic pressure, resulting in greater compression of the heart, with a consequent reduction in cardiac output and cardiac index. Therefore, it is concluded that the PEEP effects of 0 cmH2O and 5 cmH2O on hemodynamics are discrete, under the proposed conditions. Keywords: mechanical ventilation, PEEP, head-down tilt, VCV, swine. Descritores: ventilação mecânica, PEEP, posição de Trendelenburg, suínos.

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.

Brain pathology caused in the neonatal macaque by short and prolonged exposures to anticonvulsant drugs

Barbiturates and benzodiazepines are potent GABAA receptor agonists and strong anticonvulsants. In the developing brain they can cause neuronal and oligodendroglia apoptosis, impair synaptogenesis, inhibit neurogenesis and trigger long-term neurocognitive sequelae. In humans, the vulnerable period is projected to extend from the third trimester of pregnancy to the third year of life.Infants with seizures and epilepsies may receive barbiturates, benzodiazepines and their combinations for days, months or years. How exposure duration affects neuropathological sequelae is unknown. Here we investigated toxicity of phenobarbital/midazolam (Pb/M) combination in the developing nonhuman primate brain.Neonatal rhesus monkeys received phenobarbital intravenously, followed by infusion of midazolam over 5 (n = 4) or 24 h (n = 4). Animals were euthanized at 8 or 36 h and brains examined immunohistochemically and stereologically.Treatment was well tolerated, physiological parameters remained at optimal levels. Compared to naïve controls, Pb/M exposed brains displayed widespread apoptosis affecting neurons and oligodendrocytes. Pattern and severity of cell death differed depending on treatment-duration, with more extensive neurodegeneration following longer exposure. At 36 h, areas of the brain not affected at 8 h displayed neuronal apoptosis, while oligodendroglia death was most prominent at 8 h. A notable feature at 36 h was degeneration of neuronal tracts and trans-neuronal death of neurons, presumably following their disconnection from degenerated presynaptic partners.These findings demonstrate that brain toxicity of Pb/M in the neonatal primate brain becomes more severe with longer exposures and expands trans-synaptically. Impact of these sequelae on neurocognitive outcomes and the brain connectome will need to be explored.

Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial)

Background: Depression is a common psychiatric disorder that has become the leading cause of disability worldwide. The standard medical care for depression over the past 50 years has focused on monoamine neurotransmitters. These treatments can take weeks to take effect, highlighting the need for novel treatment strategies. One such approach may be ketamine. Ketamine acts as an antagonist of the N-methyl-D-asparate receptor and thus targets the excitatory amino acid neurotransmitter glutamate. Interestingly, at sub-anaesthetic doses, a single infusion of ketamine can elicit a rapid, though transient, antidepressant response. Methods: The aim of this study was to conduct a pragmatic randomised controlled pilot trial of four once-weekly ketamine infusions as an adjunctive therapy for depression. The main objective was to assess trial procedures to inform a future definitive trial. The primary clinical outcome was the 24-item Hamilton Rating Scale for Depression (HRSD-24). Trial participants were patients admitted to St Patrick’s Mental Health Services for treatment of a depressive episode. They underwent usual inpatient care as prescribed by their treating team. Consented participants were randomly allocated to a four-week course of either once-weekly ketamine (0.5mg/kg) or midazolam (0.045mg/kg) infusions given over 40 minutes and with 12 weeks follow-up. Results: In total, 1581 admissions to St Patrick’s Hospital were assessed for eligibility over nine months, with 125 (8%) meeting criteria, with 25 (20%) providing consent. In total, 13 were randomly assigned to the ketamine arm and 12 to the midazolam arm. There were no major differences in HRSD-24 scores between the two groups. The infusions were generally safe and well tolerated. Conclusions: This is the first pragmatic pilot trial of adjunctive serial ketamine infusions for hospitalised depression, an important possible use of ketamine. This study suggests that a definitive trial of adjunctive ketamine is feasible. Trial registration: ClinicalTrials.gov NCT03256162 21/08/2017; EudraCT 2016-004764-18 30/11/2016.

Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial).

Background: Depression is a common psychiatric disorder that has become the leading cause of disability worldwide. The standard medical care for depression over the past 50 years has focused on monoamine neurotransmitters. These treatments can take weeks to take effect, highlighting the need for novel treatment strategies. One such approach may be ketamine. Ketamine acts as an antagonist of the N-methyl-D-asparate receptor and thus targets the excitatory amino acid neurotransmitter glutamate. Interestingly, at sub-anaesthetic doses, a single infusion of ketamine can elicit a rapid, though transient, antidepressant response. Methods: The aim of this study was to conduct a pragmatic randomised controlled pilot trial of four once-weekly ketamine infusions as an adjunctive therapy for depression. The main objective was to assess trial procedures to inform a future definitive trial. The primary clinical outcome was the 24-item Hamilton Rating Scale for Depression (HRSD-24). Trial participants were patients admitted to St Patrick's Mental Health Services for treatment of a depressive episode. They underwent usual inpatient care as prescribed by their treating team. Consented participants were randomly allocated to a four-week course of either once-weekly ketamine (0.5mg/kg) or midazolam (0.045mg/kg) infusions given over 40 minutes and with 12 weeks follow-up. Results: In total, 1581 admissions to St Patrick's Hospital were assessed for eligibility over nine months, with 125 (8%) meeting criteria, with 25 (20%) providing consent. In total, 13 were randomly assigned to the ketamine arm and 12 to the midazolam arm. There were no major differences in HRSD-24 scores between the two groups. The infusions were generally safe and well tolerated. Conclusions: This is the first pragmatic pilot trial of adjunctive serial ketamine infusions for hospitalised depression, an important possible use of ketamine. This study suggests that a definitive trial of adjunctive ketamine is feasible. Trial registration: ClinicalTrials.gov NCT03256162 21/08/2017; EudraCT 2016-004764-18 30/11/2016.

Continuous rate infusion of midazolam as emergent treatment for seizures in dogs.

BackgroundMidazolam delivered by continuous rate infusion (CRI) might be effective in dogs with cluster seizures (CS) or status epilepticus (SE).ObjectiveTo describe the use and safety of midazolam CRI in dogs with CS or SE.AnimalsOne‐hundred six client‐owned dogs presenting to a veterinary teaching hospital with CS or SE.MethodsRetrospective review of medical records for dogs with CS or SE treated with a midazolam CRI.ResultsSeventy‐nine dogs presented with CS and 27 dogs had SE. Seizure control was achieved in 82/106 dogs (77.4%) receiving a midazolam CRI. The median dose associated with seizure control was 0.3 mg/kg/h (range, 0.1‐2.5 mg/kg/h). The median duration of CRI was 25 hours (range, 2‐96 hours). Seizures were controlled in 34/40 dogs (85%) with idiopathic epilepsy, 32/43 dogs (74%) with structural epilepsy, 12/16 dogs (75%) with unknown epilepsy, and 4/7 dogs (57%) with reactive seizures (P = .20). Seizure control was achieved in 81% of dogs with CS and 67% in dogs with SE (P = .18). Dogs with idiopathic/unknown epilepsy were more likely to survive than those with structural epilepsy (87% vs 63%, P = .009). Adverse effects were reported in 24 dogs (22.6%) and were mild in all cases.Conclusions and Clinical ImportanceMidazolam CRI is apparently safe and might be an effective treatment in dogs with CS or SE.

Mystical-type experiences occasioned by ketamine mediate its impact on at-risk drinking: Results from a randomized, controlled trial.

Sub-anesthetic ketamine administration may be helpful for substance use disorders. Converging evidence suggests that the efficacy of ketamine for certain conditions may implicate a subset of its psychoactive effects. The aim of this analysis is to evaluate whether the mystical-type effects of ketamine are critical for clinical efficacy in alcohol-dependent individuals. In this secondary analysis, we determine if a subset of the psychoactive effects of ketamine, the so-called mystical-type experience, mediates the effect of ketamine, when combined with motivational enhancement therapy, on at-risk drinking behavior in alcohol-dependent individuals interested in treatment. Forty alcohol dependent adults were randomized to either a 52-minute infusion of ketamine or midazolam, which they received on a designated quit-day during the second week of a five-week motivational enhancement therapy regimen. Psychoactive effects were assessed following the infusion, and alcohol use was monitored for the subsequent 3 weeks at each twice-weekly visit. We found that ketamine leads to significantly greater mystical-type effects (by Hood Mysticism Scale) and dissociation (by Clinician Administered Dissociative States Scale) compared to the active control. Ketamine also led to significant reduction in at-risk drinking. The Hood Mysticism Scale, but not Clinician Administered Dissociative States Scale score, was found to mediate the effect of ketamine on drinking behavior. This trial adds evidence to the literature on the importance of mystical-type experiences in addiction treatment. Future research should continue to investigate the relationship between the psychoactive effects of psychedelic therapeutics and clinical outcomes for other substance use and mental health disorders.

Status Dystonicus in Children with Secondary Dystonia: Reporting 3 Cases of Cerebral Palsy, Leigh Disease and Molybodynum Co Factor Deficiency

Objective: Patients with primary and secondary dystonic syndromes occasionally develop severe episodes of generalized dystonia and rigidity which is known as status dystonicus (SD) or dystonic storm. This is a frightening hyperkinetic movement disorder and it is an emergency. Marked, rapid exacerbation of dystonia requires prompt intervention and admission in the hospital. It is critical to recognize early and differentiate dystonic storm from other hyperkinetic movement disorder as it may lead to metabolic complications such as rhabdomyolysis, leading to acute renal failure. This paper has been written to describe three cases of SD, all having secondary dystonia with different etiologies to highlight the mode of presentation, diagnosis, treatment and outcome.&#x0D; Methodology: We report 3 cases of severe secondary dystonia culminating in SD necessitating management in hospital setting. All the three cases were admitted in a tertiary care hospital and evaluated.&#x0D; Results: One patient was treated in intensive care unit. In brief 1st case was a 5 year boy with dyskinetic CP who was treated with trihexiphenidyl (THP), baclofen and midazolam infusion. Second case was a 15 month old boy, diagnosed case of mitochondrial encephalopathy (Leigh disease) who was treated with THP, baclofen, haloperidol, clonazepam and infusion midazolam. The third case was a 13 month old boy, diagnosed case of Molybdenum Cofactor deficiency who was treated with THP, tizanidine but they refused to take midazolam.&#x0D; Conclusion: In this case series, three cases with SD with different etiology have been described with clinical features, modalities of treatment and outcome.

Treatments for Convulsive and Nonconvulsive Status Epilepticus in Adults: An Expert Opinion Survey in South Korea.

Background and PurposeThe aim of this study was to survey the expert opinions on treatments for convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) in adults.MethodsForty-two South Korean epileptologists participated in this survey. They completed an online questionnaire regarding various patient scenarios and evaluated the appropriateness of medications used to treat CSE and NCSE.ResultsInitial treatment with a benzodiazepine (BZD) followed by either a second BZD or an antiepileptic drug (AED) monotherapy was the preferred treatment strategy. More than two-thirds of the experts used a second BZD when the first one failed, and consensus was reached for 84.8% of the survey items. The preferred BZD was intravenous (IV) lorazepam for the initial treatment of status epilepticus. IV fosphenytoin and IV levetiracetam were chosen for AED monotherapy after the failure of BZD. The treatments for NCSE were similar to those for CSE. Continuous IV midazolam infusion was the treatment of choice for iatrogenic coma in refractory CSE, but other AEDs were preferred over iatrogenic coma in refractory NCSE.ConclusionsThe results of this survey are consistent with previous guidelines, and can be cautiously applied in clinical practice when treating patients with CSE or NCSE.

A retrospective review for the use of palliative sedation in a regional hospital in Hong Kong.

Palliative sedation is defined as monitored use of medication intended to induce a state of decreased or absent awareness to relieve intractable suffering in a manner that is ethically acceptable to the patient, family, and health-care providers. The prevalence of palliative sedation reported ranges from 10% to 50% during in end of life care setting. There was no major review performed on the prevalence and practice of palliative sedation in Hong Kong. Besides, published guidelines and medication recommendations are developed in Caucasian settings, which may not be taken into account the cultural aspect in Chinese. Therefore, we would like to review our practice in caring terminal cancer patients to report the prevalence and practice of palliative sedation and to review factors associated with successful sedation in this group of patients. One-hundred and eighty consecutive patients with histological or radiological evidence of malignancy who died in palliative care ward from 1st July to 30th September 2017 were screened. All patients who received continuous midazolam infusion were included. Patients' demographic data, cancer disease status, laboratory results and interview records were retrieved from electronic patient records and in-patient hospital notes. The reason for sedation, background and concurrent symptoms during sedation, and the clinical notes on symptom control during the sedation period were all reviewed. All the drug records including the dose of midazolam and other concomitant drugs, duration of palliative sedation as well as the depth of sedation were assessed. Survival data estimated from the day of admission to our department until death were recorded. Three hundred and thirty-nine patient-days, contributed by 81 patients out of 180 patients (45%), with midazolam infusion were studied. There was no statistical difference in the baseline characteristics of both patient groups. Median survival since admission to oncology ward in the sedated group was 11 versus 9 days in the non-sedated group (P=0.65). The median time for patients on sedation was 32.33 hours (range, 2.91-1,240 hours). Dyspnea was the most common cause of palliative sedation (78.0%), followed by delirium (40.9%). The mean dose of midazolam infusion was 10 milligram per day (range, 5-45 mg). Deranged liver function was the only statistically significant factor associated with successful sedation after multivariate analysis. The use of palliative sedation is safe and effective in managing refractory symptoms and is not associated with worsening of survival. Deranged liver function was associated with better symptom control. The dose of midazolam and haloperidol needed for adequate symptom control were lower than suggested in Western guidelines. Further studies on the dose requirement in Chinese population are warranted. Establishing consensus and guidelines on palliative sedation in Hong Kong should be the way forward to ensure quality care to this group of patients.

Pediatric Dystonic Storm: A Hospital-Based Study.

Pediatric dystonic storm is an underrecognized entity. We aimed to evaluate the profiles of children presenting with dystonic storm in a referral hospital. Management schema and treatment responsiveness of this uncommonly reported entity were analyzed. Retrospective review of all children (up to 18 years) hospitalized with dystonic storm over 39 months in the aforementioned facility. Twenty-three children whose ages ranged from 2 years 2 months to 14 years 4 months years (median: 6 years 11 months) (males: 13, females: 11) presented with dystonic storm. The annual incidence was 0.4 per 1,000 fresh admissions with an event rate of 0.9 per 1,000 for all admissions. All had Dystonia Severity Action Plan grades 4/5 with identifiable trigger in 13 (50%). Underlying dystonic disorder preexisted in 10 (43.4%); 8 of these had cerebral palsy. Polypharmacotherapy with >4 drugs out of trihexyphenidyl, tetrabenazine, clonazepam, gabapentin, levodopa-carbidopa, trichlorophos, and melatonin was needed. Supportive care and adequate sedation helped in symptom control. All children were managed with midazolam infusion over 2-10 days (median: 5 days). Mechanical ventilation was resorted to in 6 children (3-22 days). Vecuronium and propofol were used in 3/23 (13%) and 4/23 (17%) children, respectively. Deep brain stimulation was curative in 1 child. Hospitalization ranged from 5 to 31 (median: 11) days. Although there were no deaths, rhabdomyolysis was noted in 1 child. Postdischarge, 6 (26%) children relapsed. Dystonic storm is a medical emergency mandating aggressive multimodal management. Supportive care, antidystonic drugs, and early elective ventilation alongside adequate sedation with benzodiazepines ameliorate complications. Relapses of dystonic storm are not uncommon.