Continuous Infusion Of Midazolam Research Articles

Seizures in 3 juvenile dogs after intravenous anesthetic drug withdrawal during weaning from mechanical ventilation suspected to be a sign of iatrogenic withdrawal syndrome.

To describe seizure activity in juvenile dogs successfully weaned from long-term mechanical ventilation. Three juvenile dogs (all approximately 3months old) underwent long-term mechanical ventilation with IV anesthesia for suspected noncardiogenic pulmonary edema. Within 24hours of extubation and within 10hours of discontinuing midazolam continuous infusions, all dogs experienced seizures, which is 1 sign of iatrogenic withdrawal syndrome. Each dog was treated with an anticonvulsant protocol, and none experienced seizures after being discharged. Each dog received IV anesthesia, including fentanyl, dexmedetomidine, midazolam, and propofol, during mechanical ventilation and subsequently experienced seizures after successful weaning from mechanical ventilation. Juvenile dogs may be at risk for seizures after weaning from mechanical ventilation and IV anesthesia. Neurological monitoring and further research into an appropriate weaning protocol may prove beneficial in juvenile dogs requiring prolonged anesthesia.

Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012-2021) from a University Hospital in Germany.

Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials. The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly. This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012-2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020-2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021. Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.

EFFECTS OF DETOMIDINE AND DEXMEDETOMIDINE ON PHYSIOLOGICAL PARAMETERS AND ANESTHETIC RECOVERY IN TAPIRUS TERRESTRIS ANESTHETIZED WITH KETAMINE, GLYCERYL GUAIACOL ETHER, AND MIDAZOLAM.

The aim of this study was to compare the effects of two anesthetic induction protocols for long procedures carried out in the field in Tapiridae. Sixteen tapirs were divided into two groups (n=8) receiving either detomidine (DET) or dexmedetomidine (DEX) for anesthetic induction. All animals were anesthetized by intramuscular administration of a combination of ketamine (1.5 mg/kg), midazolam (0.2 mg/kg), plus either DET (0.04 mg/kg) or DEX (0.007 mg/kg). Anesthetic maintenance was by continuous infusion of ketamine, midazolam, and glyceryl guaiacol ether at 2 mg/kg per hour, 0.1 mg/kg per hour, and 100 mg/kg per hour, respectively). The animals were kept anesthetized for a total of 50 min to allow physical examination and collection of biological material as part of a research program, and physiological variables (heart rate [HR], respiratory rate, oxyhemoglobin saturation [SpO2], rectal temperature [RT], mean arterial pressure [MAP], blood glucose [GLI], and cortisol) and electrocardiogram were recorded during anesthesia. Anesthetic recovery was monitored by two researchers who were not informed of the induction protocol group. The recorded results were statistically evaluated. In both groups there was an initial increase in MAP, which subsequently decreased; RT gradually decreased during anesthesia; HR and GLI increased throughout the procedure; SpO2 was below normal throughout the procedure. Cortisol levels were significantly higher in the DEX group than in the DET group. Also, the animals in the DEX group had a longer recovery time than those in the DET group. On the basis of the results, we conclude that the combination of alpha-2 agonists and midazolam, ketamine, and glyceryl guaicol ether is an appropriate protocol for the anesthesia of tapirs in the field. However, in moderately extended procedures oxygen supplementation is recommended. Additionally, DEX resulted in fewer cardiovascular effects and longer-lasting sedation than DET.

745: EFFECT OF BOLUS DOSES PRIOR TO UP-TITRATION OF FENTANYL OR MIDAZOLAM FOR SEDATION

Introduction: Fentanyl and midazolam are highly lipophilic agents commonly used as continuous infusions for sedation. Based on the pharmacokinetics, a bolus dose could shorten the time to achieve steady state concentrations before being maintained with an increase in the continuous infusion. Upfront bolus dosing may avoid excessive up-titration to a maximum rate leading to drug accumulation, adverse reactions, and addition of other sedatives. The purpose of this study is to compare the efficacy and safety of bolus doses versus no bolus doses prior to up-titration of fentanyl and midazolam continuous infusions for sedation in mechanically ventilated adult patients in the medical intensive care unit (MICU). Methods: This retrospective cohort study looked at adults receiving fentanyl or midazolam infusions for sedation for at least 24 hours admitted to the MICU at North Shore University Hospital from October 2021 to April 2022. The 2 cohorts are patients pre- and post-implementation of education on fentanyl and midazolam bolus doses. Patients were excluded if they were receiving concurrent neuromuscular blocking agents, had concurrent diagnosis of uncontrolled seizures, catastrophic stroke, intracranial hemorrhage, or COVID-19 as the primary diagnosis. The primary outcome of the study is duration of mechanical ventilation (MV). Results: Thirty-six patients were analyzed with 25 in the control group and 11 in the study group. More patients in the study group had history of leukemia (8% vs 45%, p=0.018) and a higher number of sedatives prior to study drug infusion (p=0.0383). There was no difference in the median duration of MV (6 vs 9 days, p=0.1179). The control group had a statistically significant lower sedation intensity score on days 1 and 2 of sedation that on average was 9.6 and 8.5 units lower, respectively. Outcomes including number of concomitant sedatives, in-hospital mortality and time to Richmond Agitation Sedation Scale (RASS) goal were not statistically significant. Adverse events were similar between groups. Conclusions: Low protocol adherence and small sample size limit the interpretation of results. Thus, larger studies would be required to assess if there is a difference in MV using the bolus vs no bolus dose titration. Next steps include further data collection and protocol reinforcement.

Inflammation and cardiovascular status impact midazolam pharmacokinetics in critically ill children: An observational, prospective, controlled study.

Altered physiology caused by critical illness may change midazolam pharmacokinetics and thereby result in adverse reactions and outcomes in this vulnerable patient population. This study set out to determine which critical illness‐related factors impact midazolam pharmacokinetics in children using population modeling. This was an observational, prospective, controlled study of children receiving IV midazolam as part of routine care. Children recruited into the study were either critically‐ill receiving continuous infusions of midazolam or otherwise well, admitted for elective day‐case surgery (control) who received a single IV bolus dose of midazolam. The primary outcome was to determine the population pharmacokinetics and identify covariates that influence midazolam disposition during critical illness. Thirty‐five patients were recruited into the critically ill arm of the study, and 54 children into the control arm. Blood samples for assessing midazolam and 1‐OH‐midazolam concentrations were collected opportunistically (critically ill arm) and in pre‐set time windows (control arm). Pharmacokinetic modeling demonstrated a significant change in midazolam clearance with acute inflammation (measured using C‐Reactive Protein), cardio‐vascular status, and weight. Simulations predict that elevated C‐Reactive Protein and compromised cardiovascular function in critically ill children result in midazolam concentrations up to 10‐fold higher than in healthy children. The extremely high concentrations of midazolam observed in some critically‐ill children indicate that the current therapeutic dosing regimen for midazolam can lead to over‐dosing. Clinicians should be aware of this risk and intensify monitoring for oversedation in such patients.

Salmonella Meningitis: a rare case in a 3-month-old infant without evident neurological sequelae

We report here the case of a 3-month-old child with an unusual case of Salmonella spp. meningitis. The disease consisted of typical features of prostration, irritability, persistent fever, and seizure. The incubation time was relatively long for non-typhoids (04 days), but, it was relatively short for typhoid strains, whose incubation takes 7 to 14 days. Intravenous ceftriaxone was started on admission. Additional measures were taken due to hemodynamic instability and status epilepticus, requiring volume expansion, continuous infusion of vasoactive amines and intravenous midazolam, and mechanical ventilation. It generally has a poor prognosis in babies with high rates of acute neurological complications (75%) and mortality (13%). However, this case was resolved without evident neurological sequelae. Periodic assessment of cognitive growth and development is essential in this patient.

Family experience of palliative sedation therapy: proportional vs. continuous deep sedation.

Some patients experience intense symptoms refractory to intensive palliative care, and palliative sedation is sometimes used. Palliative sedation may be classified into proportional and continuous deep sedation (CDS). The primary aim of this study was to compare family experience between families of patients who received proportional or CDS. A multicenter questionnaire survey was conducted involving bereaved families of cancer patients who received proportional or CDS based on a sedation protocol. Overall evaluation of sedation (satisfaction, family-perceived distress, appropriateness of timing, and patient distress) and 13-item family concerns, good death, satisfaction with care, depression, quality of care, unfinished business, and balance between symptom relief and maintaining communication were measured. Among the 2120 patients who died, 222 patients received a continuous infusion of midazolam. A sedation protocol was used in 147 patients, and questionnaires were sent to 124 families. A total of 78 responses were finally returned (proportional, 58 vs. CDS, 20). There were no significant differences in the overall evaluation, family concerns, total score of good death, satisfaction, depression, or balance between symptom relief and maintaining communication. On the other hand, some quality of care items, i.e., relationship with medical staff (P < 0.01), physical care by nurses (P = 0.04), and coordination and consistency (P = 0.04), were significantly better in the CDS group than in the proportional sedation group. Family-reported unfinished business was also better in the CDS group, with marginal significance. Family experience of CDS was not less favorable than proportional sedation, and actually rated more favorably for some elements of quality of care and unfinished business.

Electrical Impedance Tomography to Set Positive End Expiratory Pressure During Pediatric Extracorporeal Membrane Oxygenation for Respiratory Failure... Is it Feasible?

Electrical Impedance Tomography to Set Positive End Expiratory Pressure During Pediatric Extracorporeal Membrane Oxygenation for Respiratory Failure... Is it Feasible?

Treatment of Neonatal Seizures: Comparison of Treatment Pathways From 11 Neonatal Intensive Care Units

ObjectiveSeizures are a common neonatal neurologic emergency. Many centers have developed pathways to optimize management. We evaluated neonatal seizure management pathways at level IV neonatal intensive care units (NICUs) in the United States to highlight areas of consensus and describe aspects of variability. MethodsWe conducted a descriptive analysis of 11 neonatal seizure management pathways from level IV NICUs that specialize in neonatal neurocritical care including guidelines for electroencephalography (EEG) monitoring, antiseizure medication (ASM) choice, timing, and dose. ResultsStudy center NICUs had a median of 70 beds (interquartile range: 52-96). All sites had 24/7 conventional EEG initiation, monitoring, and review capability. Management pathways uniformly included prompt EEG confirmation of seizures. Most pathways included a provision for intravenous benzodiazepine administration if either EEG or loading of ASM was delayed. Phenobarbital 20 mg/kg IV was the first-line ASM in all pathways. Pathways included either fosphenytoin or levetiracetam as the second-line ASM with variable dosing. Third-line ASMs were most commonly fosphenytoin or levetiracetam, with alternatives including topiramate or lacosamide. All pathways provided escalation to continuous midazolam infusion with variable dosing for seizures refractory to initial medication trials. Three pathways also included lidocaine infusion. Nine pathways discussed ASM discontinuation after resolution of acute symptomatic seizures with variable timing. ConclusionsDespite a paucity of data from controlled trials regarding optimal neonatal seizure management, there are areas of broad agreement among institutional pathways. Areas of substantial heterogeneity that require further research include optimal second-line ASM, dosage, and timing of ASM discontinuation.

Efficacy of Proportional Sedation and Deep Sedation Defined by Sedation Protocols: A Multicenter, Prospective, Observational Comparative Study

PurposeTo investigate the efficacy of two types of palliative sedation: proportional and deep sedation, defined by sedation protocols. MethodsFrom a multicenter prospective observational study, we analyzed the data of those patients who received the continuous infusion of midazolam according to the sedation protocol. The primary endpoint was goal achievement at 4 hours: in proportional sedation, symptom relief (Integrated Palliative care Outcome Scale: IPOS ≤ 1) and absence of agitation (modified Richmond Agitation-Sedation Scale: RASS ≤ 0); in deep sedation, the achievement of deep sedation (RASS ≤ -4). Secondary endpoints included deep sedation as a result of proportional sedation, communication capacity (Communication Capacity Scale item 4 ≤ 2), IPOS and RASS scores, and adverse events. ResultsA total of 81 patients from 14 palliative care units were analyzed: proportional sedation (n = 64) and deep sedation (n = 17). At 4 hours, the goal was achieved in 77% (n = 49; 95% confidence interval: 66-87) with proportional sedation; and 88% (n = 15; 71-100) with deep sedation. Deep sedation was necessary in 45% of those who received proportional sedation. Communication capacity was maintained in 34% with proportional sedation and 10% with deep sedation. IPOS decreased from 3.5 to 0.9 with proportional sedation, and 3.5 to 0.4 with deep sedation; RASS decreased from +0.3 to -2.6, and +0.4 to -4.2, respectively. Fatal events related to the treatment occurred in 2% (n = 1) with proportional and none with deep sedation. ConclusionProportional sedation achieved satisfactory symptom relief while maintaining some patients’ consciousness, and deep sedation achieved good symptom relief while the majority of patients lost consciousness.

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.

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.

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.

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.

Assessment of midazolam pharmacokinetics in the treatment of status epilepticus

ObjectivesRefractory status epilepticus (RSE) is often treated with midazolam boluses and continuous infusions, but there is considerable variability in dosing and efficacy. We aimed to evaluate the performance of a clinical midazolam dose escalation pathway for the treatment of pediatric RSE that was designed based on a novel midazolam pharmacokinetic model. DesignProspective pharmacokinetic study of midazolam bolus and escalation of continuous midazolam infusion. SettingPediatric Intensive Care Unit in quaternary-care academic hospital. SubjectsChildren between two months to seventeen years of age who received clinically-indicated midazolam infusion for treatment of RSE. InterventionBlood sampled at regular intervals during treatment. Main study outcome measure was the accuracy of a pharmacokinetic model to predict serum midazolam concentrations. Measurements and main resultsWe analysed data from six subjects. Three subjects had serum midazolam concentrations close to those predicted by our initial model (accuracy 88.9–170.2 %) which incorporates body weight, hepatic function, and renal function. For the other three subjects, all of whom were receiving pre-existing chronic benzodiazepine therapy prior to the RSE episode, the model grossly overestimated serum concentrations (predictive error 420.3–722.5 %). Once the model was corrected for the impact of pre-existing chronic benzodiazepine use on clearance, predicted concentrations more closely reflected those measured in subjects. ConclusionWe evaluated a clinical midazolam RSE treatment pathway but discovered that the model on which the pathway was based was not accurate for all patients. We therefore developed a novel pharmacokinetic midazolam model in children with RSE treated with continuous midazolam infusion. This model incorporates body weight, hepatic and renal function, and importantly, a correction factor for pre-existing chronic benzodiazepine use. Once validated, this model may guide dosing and drive the development of more effective treatment pathways for continuous midazolam in RSE.

Iatrogenic withdrawal syndrome in specialty pediatric critical care

AimTo describe the occurrence of opioid and benzodiazepine withdrawal symptoms in a cohort of pediatric intensive care unit (PICU) patients, the characteristics of this group, and patterns of withdrawal scoring observed during medication weaning. BackgroundPatients in the PICU are a complex and vulnerable population. Opioids and benzodiazepines are routinely administered in this setting. Providers must be equipped to recognize and assess symptoms of narcotic and benzodiazepine withdrawal. MethodsA retrospective chart review was conducted to describe all patients admitted to the medical intensive care unit who received continuous infusions of morphine and midazolam during a one-year period. Patient demographics, diagnosis, and presence of co-morbidities were abstracted. The number of days on continuous infusions was measured, along with Withdrawal Assessment Tool-1 (WAT-1) scores and documented symptoms that could be associated with withdrawal. WAT-1 scoring ranges from 0 to 12, a WAT-1 score of 3 or higher is considered to indicate clinically significant withdrawal symptoms. Descriptive statistics were utilized to summarize demographic and clinical variables. ResultsAmong 60 cases, patient ages ranged 5 weeks to 29 years (median 3.5 years). Eighty percent of patients had a primary respiratory diagnosis and 88.3% had one or more co-morbidities. Forty-four patients (73.3%) had symptoms consistent with withdrawal. Thirty-one percent of patients had a maximum WAT-1 score between 3 and 8. The majority of patients (55%) had a history of opioid and/or benzodiazepine exposure. ConclusionsThe information learned highlights the need for ongoing conversation and continued study of how best to assess and manage withdrawal syndrome in pediatric critical care environments.

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.

Protocolo anestésico para ressecção parcial da parede torácica seguida de reconstrução em cães: relato de dois casos

O presente trabalho relata o protocolo anestésico utilizado em dois cães submetidos à cirurgia de ressecção e reconstrução da parede torácica devido a neoplasmas, no Hospital Veterinário Roque Quagliato do Centro Universitário das Faculdades Integradas de Ourinhos, São Paulo. Uma cadela poodle de 10 anos e um cão rottweiler de um ano e três meses foram submetidos à anestesia geral com isofluorano, bloqueio intercostal de, respectivamente, seis e sete espaços intercostais com lidocaína 2% e bupivacaína 0,5% e infusão contínua de morfina (0,1 mg/kg/h), lidocaína (50 μg/kg/minuto) e midazolam (0,1 mg/ kg/h). No período pós-operatório imediato, ambos receberam administração peridural de morfina 0,2 mg/kg e fentanila 2 μg/kg diluídos com NaCl 0,9% para 0,3 mL/kg. Um tubo de analgesia foi deixado durante as 48 horas subsequentes na ferida cirúrgica para administração de lidocaína e bupivacaína em total de uma dose tóxica por dia, fracionada para cinco aplicações. A prescrição analgésica pós-operatória constituiu-se de tramadol 4 mg/kg e dipirona 25 mg/kg a cada oito horas durante sete dias, juntamente com meloxicam 0,1 mg/kg a cada 24 horas durante três dias. Os animais recuperaram-se tranquilamente e não foram observados sinais de dor ao longo dos sete dias subsequentes. Recomenda-se o protocolo relatado para cirurgias de ressecção da parede torácica em cães.&#x0D;