The Effect of Intravenous Dexamethasone and Dexmedetomidine on Analgesia Duration of Supraclavicular Brachial Plexus Block: A Randomized, Four-Arm, Triple-Blinded, Placebo-Controlled Trial

Intravenous dexamethasone and dexmedetomidine, in conjunction with peripheral nerve blockade, have each been reported to prolong the duration of analgesia. This study tested whether combined use further prolongs analgesia duration after supraclavicular brachial plexus block (BPB) in patients undergoing orthopedic upper extremity surgery. One hundred twenty patients were randomized 1:1:1:1 to Control (saline bolus and midazolam infusion [0.05 mg/kg loading, 20 µg/kg/h thereafter]); DMED (saline bolus and dexmedetomidine infusion [1 μg/kg loading, 0.4 μg/kg/h thereafter]); DEXA (dexamethasone [10 mg] bolus and midazolam infusion); and DMED-DEXA (dexmedetomidine infusion and dexamethasone bolus) groups. The primary outcome was the duration of postoperative analgesia, defined as the time from the end of the BPB to the first dose of analgesia via a patient-controlled device. Median (interquartile range) times to first dose of analgesia in the Control, DMED, DEXA, and DMED-DEXA groups were 8.1 (6.2–11.6), 9.0 (8.1–11.3), 10.7 (8.1–20.5), and 13.2 (11.5–19.1) hours, respectively (p < 0.001). Pairwise comparisons showed significant prolongation of analgesia in the DEXA included groups compared with the non-DEXA included groups (DEXA vs. control, p = 0.045; DEXA vs. DMED, p = 0.045; DMED-DEXA vs. control, p < 0.001; DMED-DEXA vs. DMED, p < 0.001). A mixed effect model showed that dexamethasone was the only significant factor for the prolongation of analgesia (p < 0.001). Intravenous dexamethasone prolonged the analgesia duration of supraclavicular BPB after orthopedic upper extremity surgery. The concurrent use of mild to moderate sedation dose of intravenous dexmedetomidine in addition to intravenous dexamethasone showed no additional benefit to the prolongation of analgesia.

A Man With Flulike Symptoms and Hemorrhagic Brain Lesions

A 52-year-old man is admitted to a neurosciences intensive care unit during winter for management of seizures requiring mechanical ventilation. Two days earlier he reported cough and myalgia. He was found seated on the couch with altered mental state and was minimally responsive. Upon arrival to the emergency department he was febrile at 38.8 °C and tachycardic. Complete blood cell count showed leukocytosis (11.1×109 cells/L, neutrophilic predominance). Computed tomography of the head showed an area of hypodensity in the left temporal lobe. During computed tomography, the patient had generalized convulsions requiring lorazepam, fosphenytoin, and levetiracetam, followed by initiation of a continuous midazolam infusion before seizures were controlled. He was started on broad-spectrum antimicrobials, including acyclovir, and a lumbar puncture was performed. Cerebrospinal fluid protein concentration was 196 mg/dL, and he had 10 white blood cells/µL with lymphocyte predominance. There was no hypoglycorrhachia. After 24 hours, the patient was weaned from the midazolam infusion and maintained on levetiracetam monotherapy. He was extubated but remained encephalopathic. Magnetic resonance imaging performed the day after admission demonstrated numerous T2 hyperintense lesions throughout both cerebral hemispheres including both mesial temporal lobes and right thalamus. Nasopharyngeal polymerase chain reaction was positive for influenza virus A, which was later typed further and identified as pandemic 2009 H1N1 virus. A diagnosis of influenza-associated encephalopathy/encephalitis was made. The patient was treated with oseltamivir, as well as high-dose intravenous methylprednisolone. His encephalopathy gradually improved. Repeated imaging at 3-month follow-up showed resolution of the previously seen abnormalities. His neurologic examination was normal. Postinfectious or parainfectious autoimmunity syndromes refer to neurologic signs and symptoms that develop during or after an infection but are not thought to be caused by direct infection of the nervous system.

Midazolam Infusion and Disease Severity Affect the Level of Sedation in Children: A Parametric Time-to-Event Analysis

Aim In critically ill mechanically ventilated children, midazolam is used first line for sedation, however its exact sedative effects have been difficult to quantify. In this analysis, we use parametric time-to-event (PTTE) analysis to quantify the effects of midazolam in critically ill children. Methods In the PTTE analysis, data was analyzed from a published study in mechanically ventilated children in which blinded midazolam or placebo infusions were administered during a sedation interruption phase until, based on COMFORT-B and NISS scores, patients became undersedated and unblinded midazolam was restarted. Using NONMEM® v.7.4.3., restart of unblinded midazolam was analysed as event. Patients in the trial were divided into internal and external validation cohorts prior to analysis. Results Data contained 138 events from 79 individuals (37 blinded midazolam; 42 blinded placebo). In the PTTE model, the baseline hazard was best described by a constant function. Midazolam reduced the hazard for restart of unblinded midazolam due to undersedation by 51%. In the blinded midazolam group, time to midazolam restart was 26 h versus 58 h in patients with low versus high disease severity upon admission (PRISM II < 10 versus > 21), respectively. For blinded placebo, these times were 14 h and 33 h, respectively. The model performed well in an external validation with 42 individuals. Conclusion The PTTE analysis effectively quantified the effect of midazolam in prolonging sedation and also the influence of disease severity on sedation in mechanically ventilated critically ill children, and provides a valuable tool to quantify the effect of sedatives. Clinical trial number and registry URL: Netherlands Trial Register, Trial NL1913 (NTR2030), date registered 28 September 2009 https://www.trialregister.nl/trial/1913.

Asystole in 2 Pediatric Patients During Dexmedetomidine Infusion

Introduction: Bradycardia is a known side effect of dexmedetomidine. Reports of sinus pauses or asystole, however, are rare. We present 2 cases of pediatric patients who developed asystole on a dexmedetomidine infusion. Summary of Cases: An 8-week-old male with RSV bronchiolitis and acute hypoxemic respiratory failure was started on dexmedetomidine for sedation at 0.2 mcg/kg/h with a maximum dose of 0.7mcg/kg/h. On Hospital day (HD) 4, on dexmedetomidine at 0.7 mcg/kg/h, he developed intermittent episodes of bradycardia with heart rates in the 60 s. Echocardiogram on HD 6 showed normal function. On HD 7, he began having periods of asystole lasting up to 6 seconds. Dexmedetomidine was discontinued, with the resolution of episodes of asystole after 6 hours. A 27-month-old male with a congenital left diaphragmatic hernia and pulmonary hypertension who had been weaned off sildenafil 6 months earlier underwent re-repair of left diaphragmatic hernia. Postoperatively he remained intubated and paralyzed. Dexmedetomidine was started at 0.3 mcg/kg/h for sedation, with a maximum dose of 1.2 mcg/kg/h. An echocardiogram on HD 3 showed good function with mild to moderate pulmonary hypertension. That evening, with dexmedetomidine at 1.1 mcg/kg/h, he developed a 15 second period of asystole requiring CPR. Dexmedetomidine was discontinued, and he was started on a midazolam infusion with no further episodes. Discussion: Both cases occurred in patients without cardiac conduction defects or on negative chronotropic or sympatholytic medications that have been associated with dexmedetomidine-induced asystole. We hypothesize that both episodes of asystole were due to increased patient-related vagal tone exacerbated by dexmedetomidine.

Status dystonicus in children: Treat the precipitating factors

Status dystonicus (SD) is a life-threatening movement disorder associated with significant morbidity and requires immediate and urgent intervention. It usually develops from both primary and secondary dystonias and rarely can be a complication of symptomatic insults such as infections, brain insults, or drugs. Compared to adults, it is seen more commonly in children due to the risk of many trigger factors and vulnerability of the developmental brain. Due to the delay in the identification and prevention of the triggering factors, nowadays most children require intensive care. Here, we report a 1-year-old boy, who was a known case of dyskinetic cerebral palsy, presented with increased twisting movements after an episode of febrile illness. The SD partially resolved after midazolam infusion, however, after treating the triggering factors (constipation and pneumonia), the SD resolved completely.

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<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.

Midazolam infusion and disease severity affect the level of sedation in children: a parametric time-to-event analysis of data from the ‘daily sedation interruption in critically ill children’ trial

Aim In critically ill mechanically ventilated children, midazolam is used first line for sedation, however its sedative effects have been difficult to quantify for which novel quantification methods are still required. In this analysis, we use parametric time-to-event (PTTE) analysis to quantify the effects of midazolam in critically ill children. Methods For the PTTE analysis, data was analyzed from a published sedation interruption study in mechanically ventilated critically ill children. In this study, blinded midazolam or placebo infusions were administered during the sedation interruption phase until, based on COMFORT-B and NISS scores, patients became undersedated and unblinded midazolam was restarted. Using NONMEM® v.7.4.3.,the restart of unblinded midazolam was analysed as a clinical event, followed by internal and external validation. Results Data contained 138 events from 79 individuals (37 blinded midazolam; 42 blinded placebo). In the PTTE model, a constant function best described the baseline hazard. The use of midazolam reduced the hazard for restart of unblinded midazolam due to undersedation by 51%. In the blinded midazolam group, time to midazolam restart was 26 h versus 58 h in patients with low versus high disease severity upon admission (PRISM II <10 versus > 21), respectively. For blinded placebo these times were 14 h and 33 h, respectively. The model performed well in an external validation with 42 individuals. Conclusion The PTTE analysis effectively quantified the effect of midazolam and the influence of disease severity on sedation in mechanically ventilated critically ill children and provides a valuable tool to quantify sedative efficacy

Pediatric dystonic storm : A hospital-based study

Background:Pediatric dystonic storm is an under-recognized 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.Methods:Retrospective review of all children (up to 18 years) hospitalized with dystonic storm over 39 months in the aforementioned facility.Results:23 children aged 2year 2months to 14 year 4 months years (median:6 year 11 months)(males: 13, females:11) presented with dystonic storm. Annual incidence was 0.4 per 1000 fresh admissions with event rate of 0.9 per 1000 for all admissions. All had Dystonia Severity Action Plan (DSAP) grades 4/5 with identifiable trigger in 13 (50%). Underlying dystonic disorder pre-existed in 10(43.4%); 08 of these had Cerebral Palsy . Polypharmacotherapy with >4 drugs out of trihexyphenydyl, tetrabenazine, clonazepam, gabapentin, levodopa-carbidopa, triclophos and melatonin were 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 5-31(median: 11) days. While there were no deaths, rhabdomyolysis was noted in 1 child. Post discharge,6(26%) children relapsed.Conclusions:Dystonic storm is a medical emergency mandating aggressive multimodal management. Supportive care, anti-dystonic drugs, early elective ventilation alongside adequate sedation with benzodiazepines ameliorate complications. Relapses of dystonic storm are not uncommon.