Midazolam compared with ketamine for invasive procedures

The combination of ketamine and topical placebo cream was compared with the combination of midazolam and topical lidocaine-prilocaine cream (EMLA) in 13 children with leukaemia undergoing bone marrow punctures. This double-blind, randomized, crossover study showed that the children prefer midazolam and EMLA as sedation for invasive procedures and that some parents and the nursing staff have doubts because of the anxiety during the procedure and the physical restraint that often is necessary during midazolam and EMLA. Both methods cause several, more or less unpleasant, side effects.     

Use of intramuscular ketamine for endoscopy sedation in children

OBJECTIVE: To report the experience of the use of intramuscular (IM) ketamine for endoscopy sedation in children. METHODOLOGY: Children over 6 months of age scheduled for elective endoscopy - esophagogastroduodenoscopy (EGD), bronchoscopy and nasopharyngolaryngoscopy (NPL) were enrolled for (2 mg/kg to 3 mg/kg) intramuscular ketamine sedation. A repeated dose of 2 mg/kg intramuscular ketamine was administered to those who failed the first sedation. Alternative sedation (intravenous midazolam and fentanyl) was given to children who failed ketamine sedation twice. Sedation was regarded as successful if the procedure was completed by endoscopist with a single dose of ketamine. RESULTS: Sixty children were enrolled for the study. Overall success rate in our patients was 78.3%. Failure rate in infants was 50%, i.e. 4 out of 8. For children aged 1-7, the failure rate was 32%. Failure rate dropped markedly to 6.7% for those older than 7 years of age, and it showed significant difference when compared with the other two groups. Two cases of laryngospasm were experienced in the present study. CONCLUSION: Intramuscular ketamine is an effective medication for sedation in endoscopy undertaken in children over age 7 years, but it should be avoided with children under age 7 because of the high failure rate.     

Sedation and analgesia for critically ill children

Effective analgesia and sedation in the paediatric intensive care unit (PICU) encompasses the provision of physical comfort and caring for the psychological well-being of critically ill children. In the UK the most commonly used sedative and analgesic agents for critically ill children are midazolam and either morphine or fentanyl. Consensus clinical practice guidelines for the provision of sedation and analgesia in critically ill children were published in 2006 by the UK Paediatric Intensive Care Society, and an ESPNIC position statement on clinical recommendations for pain, sedation, withdrawal and delirium assessment in critically ill infants and children was published in 2016: Despite this, considerable variation in practice persists. Pain experienced early in life may result in long-term changes in neurosensory function and there are also concerns that sedative and analgesic agents may themselves be associated with developmental neurotoxicity, particularly amongst neonates, and adverse psychological outcomes in survivors of critical care. Validated tools for assessment of withdrawal syndrome and delirium are available and this article will briefly discuss these and how to use them in clinical practice. The most important single factor in reducing avoidable psychological morbidity in survivors of PICU is to minimize the administered doses of sedative and analgesic agents.     

Use of oral midazolam in pediatric upper gastrointestinal endoscopy

Background: The purpose of this prospective, randomized study was to compare the safety and efficacy of oral versus i.v. midazolam in providing sedation for pediatric upper gastrointestinal (GI) endoscopy. Methods: Sixty‐one children (age <16 years) scheduled for upper GI endoscopy were studied. Patients were randomly assigned to receive oral or i.v. midazolam. Measurements were made and compared for vital signs, level of sedation, pre‐ and post‐procedure comfort, anxiety during endoscopy, ease of separation from parents, ease and duration of procedure, and recovery time. Results: Patients were aged 1–16 years (mean 7.5 ± 3.42 years); 30 patients received oral medication, and 31 received i.v. medication. There were no statistically significant differences in age or gender between groups. There were no significant differences in level of sedation, ease of separation from parents, ease of ability to monitor the patient during the procedure, heart rate, systolic arterial pressure, or respiratory rate. Oxygen saturation was significantly lower in the i.v. group than the oral group 10 and 30 min after removal of the endoscope, and recovery time was longer in the oral than the i.v. group. Conclusions: Oral administration of midazolam is a safe and effective method of sedation that significantly reduces anxiety and improves overall tolerance for children undergoing esophagogastroduodenoscopy.     

Efficacy and safety of a mixture of ketamine, midazolam and atropine for procedural sedation in paediatric oncology: a randomised study of oral versus intramuscular route

Aim:   To evaluate the efficacy and safety of a mixture of ketamine, midazolam and atropine given orally by comparing the same mixture given through the intramuscular route in children with malignancy undergoing minor invasive procedures.
Methods:   Sixty children, aged between 1 and 10 years, scheduled to undergo minor procedures were randomised into two groups to receive a mixture of ketamine (6 mg/kg), midazolam (0.05 mg/kg) and atropine (0.02 mg/kg) intramuscularly (Group 1) or ketamine (10 mg/kg), midazolam (0.2 mg/kg) and atropine (0.05 mg/kg) orally (Group 2). Sedation score, observer-rated visual analogue scale for pain were noted by an observer blinded to the route of drug administration.
Results:   Optimum sedation was present in all children in both groups after drug administration, with Group 1 being more deeply sedated than Group 2 at the start of the procedure. Supplementation with intravenous ketamine was required in four children in Group 1 and eight children in Group 2 ( P  = 0.33). The mean (±SD) observer-rated visual analogue scale for pain during the procedure was 8.33 (±15.99) and 9.33 (±16.39) in Group 1 and Group 2, respectively ( P  = 0.892). One patient in Group 1 had vomiting after the procedure. There were no differences in proportion of patients with hallucinations and nystagmus in both groups.
Conclusions:   A mixture of ketamine, midazolam and atropine given orally provides sedation and analgesia similar to that produced by the same drugs given intramuscularly. It offers advantage over the intramuscular route as it is painless and can be given for minor paediatric oncology procedures with appropriate monitoring.     

Comparative study of intranasal midazolam and intravenous diazepam sedation for procedures and seizures

Objective To evaluate the safety and efficacy of intranasal midazolam for seizures and various procedures. Methods Prospective randomized study. Total 125 children of all ages of either sex, for seizure episode (n-76) and various invasive and non-invasive procedures (n-49) received either intranasal midazolam (0.2 mg/Kg) or intravenous diazepam (0.3 mg/Kg). Results Mean time from arrival at hospital to starting treatment was significantly shorter in midazolam group compared to diazepam group [2.34±0.90; minute vs 4.61±1.08 minute p<0.001]. Mean time to control seizures after arrival in hospital was significantly shorter in midazolam group compared to diazepam group [5.25±0.86 minute vs 6.51±1.06 minute p<0.001]. Conclusion Midazolam by the intranasal route provides safe and equally effective non-invasive method of sedation for procedures and seizures.     

Use of Ketofol for procedural sedation and analgesia in children with hematological diseases

Background: The aim of this study was to evaluate the effectiveness and safety of intravenous ketamine–propofol admixture (“ketofol”) in the same syringe for procedural sedation and analgesia in children undergoing bone marrow aspiration. Methods: This was a prospective, observational pilot study. Patients aged between 4 and 12 years requiring sedation for bone marrow aspiration were included. Ketofol (1 : 1 mixture of ketamine 10 mg/mL and propofol 10 mg/mL) was given intravenously in 0.5 mg/kg aliquots each with a 1‐min interval and titrated to reach sedation levels of 3 or 4 (Ramsay score). The primary outcome was patient satisfaction with the degree of sedation. Secondary outcomes included injection pain, total sedation time, recovery time, hemodynamic and respiratory parameters, and adverse events. Results: A total of 20 patients were enrolled in the study. The median total dose of ketofol administered was 1.25 mg/kg each of propofol and ketamine (95%CI 0.77–2 mg/kg). The median score on the visual analog scale was 0 (extremely comfortable) (0–1.5; 95%CI 0.2–2.2). Median recovery time was 23 min (20.5–28 min; 95%CI 17.1–51.2). The incidence of injection pain was 2/20. Two patients had transient diplopia and one child reported dreams. No patients had hypotension, vomiting or required airway intervention. Conclusion: Ketofol provided effective sedation, which was reflected in the high degree of satisfaction recorded by children requiring procedural sedation and analgesia for bone marrow aspiration. We also observed rapid recovery and no clinically significant complications. A large number of patients is required to evaluate and validate these findings.     

Efficacy and safety of intravenous midazolam and ketamine as sedation for therapeutic and diagnostic procedures in children

OBJECTIVE: We have used the combination of midazolam, a short-acting benzodiazepine, and ketamine, a "dissociative anesthetic," to provide conscious sedation for invasive or lengthy procedures. METHODS: A total of 350 procedures (74 lumbar punctures, 97 bone marrow aspirations or biopsies, 84 radiotherapy sessions, and 95 imaging studies) were performed on 68 children, 4 months to 17 years of age, in both inpatient and ambulatory settings. All patients had an intravenous line in place and were monitored for heart rate and O2 saturation by pulse oximetry for the duration of the procedure and recovery time. Blood pressure was monitored periodically (every 5 to 30 minutes). Oxygen and suction equipment was available during the procedure. In addition to the individual performing the procedure, a second staff member trained in airway management (eg, physician, nurse practitioner, or registered nurse) was present to monitor vital signs and respiratory status. Patients were sedated initially with midazolam (0.05 to 0.1 mg/kg intravenously; maximum single dose of 2 mg, maximum total dose of 4 mg), followed by ketamine (1 to 2 mg/kg intravenously). During lengthy procedures, additional doses of ketamine (0.5 to 1 mg/kg) were given as necessary. Effectiveness of the sedation, recovery time, and adverse events associated with the sedative regimen were documented. RESULTS: All patients were effectively sedated with this regimen. Four patients experienced transient decrease in O2 saturation (<85%) requiring temporary interruption of the procedure and oxygen by blow-by; the procedure was subsequently completed without incident in each case. Two patients experienced significant agitation during recovery from sedation. This side effect resolved spontaneously after 5 to 10 minutes in one patient and was effectively treated with diphenhydramine hydrochloride in the other. Twenty-four lumbar punctures were associated with transient decrease in O2 saturation (88% to 92%), which improved by relief of neck flexion and/or blow-by oxygen. No hypotension, bradycardia, or respiratory depression requiring respiratory support or reversal of sedation was noted. Anesthesia recovery time ranged from <15 minutes to 120 minutes with >70% of patients recovering within 30 minutes. Most patients demonstrated an increase in oral secretions requiring occasional suctioning. Transient sleep disturbances were reported in only two patients. CONCLUSIONS: This sedative regimen of intravenous midazolam and ketamine was found to be safe and effective. Its use has greatly reduced patient and parent anxiety for diagnostic and therapeutic procedures.     

Sedation with intranasal midazolam of Angolan children undergoing invasive procedures

Aim: Ambulatory surgery is a daily requirement in poor countries, and limited means and insufficient trained staff lead to the lack of attention to the patient’s pain. Midazolam is a rapid‐onset, short‐acting benzodiazepine which is used safely to reduce pain in children. We evaluated the practicability of intranasal midazolam sedation in a suburban hospital in Luanda (Angola), during the surgical procedures. Methods: Intranasal midazolam solution was administered at a dose of 0.5 mg/kg. Using the Ramsay’s reactivity score, we gave a score to four different types of children’s behaviour: moaning, shouting, crying and struggling, and the surgeon evaluated the ease of completing the surgical procedure using scores from 0 (very easy) to 3 (managing with difficulty). Results: Eighty children (median age, 3 years) were recruited, and 140 surgical procedures were performed. Fifty‐two children were treated with midazolam during 85 procedures, and 28 children were not treated during 55 procedures. We found a significant difference between the two groups on the shouting, crying and struggling parameters (p < 0.001). The mean score of the ease of completing the procedures was significantly different among the two groups (p < 0.0001). Conclusion: These results provide a model of procedural sedation in ambulatory surgical procedures in poor countries, thus abolishing pain and making the surgeon’s job easier.     

Sedation with midazolam and ketamine for invasive procedures in children with malignancies and hematological disorders: a prospective study with reference to the sympathomimetic properties of ketamine

Different pharmacological agents have been used for sedation in children undergoing invasive procedures. The authors prospectively evaluated the efficacy, the occurrence of adverse side effects, and cardiovascular parameters in midazolam and ketamine sedation for invasive procedures in children with malignancies and hematological disorders. A total of 183 invasive procedures were performed on 63 children (mean age 9.2 +/- 5.2 years). Intravenous sedation consisted of 0.1 mg midazolam/kg and 1.0 mg ketamine/kg. Incremental dosages of ketamine (0.33 mg/kg) were given if necessary to maintain deep sedation. Systolic and diastolic blood pressure, heart rate, and oxygen saturation were recorded. All 183 invasive procedures were successfully completed with satisfactory sedation levels in 170 procedures (92.9%; 95% CI:88.2-96.2%). In 33 procedures (18%; 95% CI: 12.8-24.4%) sedation was associated with side effects, the most common being oxygen desaturation. One patient experienced a transient episode of laryngospasm. There was a significant increase in both systolic and diastolic blood pressure and heart rate after ketamine medication (p <.01). Procedure and recovery time were correlated to ketamine dosage (p <.01). The combination of midazolam and ketamine is efficacious in achieving deep sedation for painful invasive procedures. Considering the possibility of potentially serious respiratory complications it should be performed only by physicians who are trained in advanced airway management and life support. As opposed to many other sedative drugs with cardio-depressant properties, ketamine causes a rise in both systolic and diastolic blood pressure, and heart rate.     

Oral versus rectal midazolam as a pre-anaesthetic sedative in children receiving dental treatment under general anaesthesia

Dental treatment in children who are too young or too apprehensive to cooperate is often performed under sedation. In Sweden, the tradition has been to administer sedatives rectally in small children, but oral liquid sedation is now increasingly used. AIM: To compare the sedative effects of oral and rectal administration of midazolam in children undergoing dental treatment under general anaesthesia and to assess acceptance of sedative administration, acceptance of application of the facemask, and amnesia. METHODS: Fifty children aged 2-7 y were randomly allocated to receive either liquid oral or rectal sedation, with 25 children in each group. RESULTS: The sedative effect of rectal administration was higher, but not statistically significantly, than that of oral administration (p = 0.07). No significant differences in acceptance of sedative administration, acceptance of mask application or amnesia were found between the groups. CONCLUSION: Both the oral and the rectal routes can in most cases be appropriate. However, the better sedative effect of rectal administration of midazolam makes it a more favourable route in pre-cooperative and non-compliant children.     

End-tidal carbon dioxide monitoring during sedation with a combination of midazolam and ketamine for children undergoing painful, invasive procedures.

BACKGROUND: Previous studies evaluating the respiratory effects of sedation regimens have focused on events such as a decline in O2 saturation or apnea. The current study used both end-tidal carbon dioxide (ETCO2) monitoring and pulse oximetry to evaluate the respiratory effects of midazolam and ketamine. METHODS: Fifty children who required sedation during invasive procedures formed the cohort for the study. During sedation, ETCO2 was sampled from nasal cannulae of spontaneously breathing patients and measured by a side-stream aspirating infrared device. RESULTS: During the procedure, O2 saturation decreased by 3% or more in three patients. Supplemental oxygen at 2 liters per minute was administered to these patients. The lowest oxygen saturation was 84%. During the total of 767 minutes of monitoring, there were 3068 ETCO2 values recorded. The high ETCO2 values ranged from 37 to 53 mmHg (40.5 +/- 3.3 mmHg). Ninety percent, or 2760, of the values were 40 mmHg or less, 7% or 214 were between 41 and 45 mmHg, 3% or 92 were between 46 and 49 mmHg, and 2 isolated values were greater than 50 mmHg. One episode of airway obstruction was identified by noting cessation of the ETCO2 waveform. This was relieved by repositioning the patient's airway. The three episodes of O2 desaturation, two ETCO2 values greater than 50 mmHg, and the episode of upper airway obstruction all occurred in three patients. Two of these patients had trisomy 21 with macroglossia, and the third had had a recent upper respiratory infection and a history of tonsillar hypertrophy. CONCLUSION: The incidence of adverse cardiorespiratory events associated with the current sedation regimen of midazolam-ketamine is lower than that reported with other commonly used regimens. The addition of ETCO2 monitoring provides an additional monitor to allow for early detection of airway obstruction or subclinical degrees of respiratory depression.     

Oral ketamine for radiotherapy in children with cancer

Children coming for radiotherapy under sedation usually get repeated injections, which cause distress to both the child and the parents. A prospective study was conducted to evaluate the efficacy of oral ketamine for sedation for radiotherapy (RT) in children with cancer. Ten children who received 49 sittings of RT were given 8–15 mg/kg body weight of oral ketamine. The onset time, recovery time, efficacy of sedation and incidence of abnormal movements were compared with another group of 8 children, who received intramuscular ketamine in the dose of 6 mg/kg for a total of 28 sittings of RT. Onset time and recovery time were significantly longer in oral ketamine group as compared to the intramuscular group (p<0.001). Limb movements in patients receiving oral ketamine necessitated further supplement of sedation and interruption of RT. These drawbacks discourage use of oral ketamine as a good sedative for radiotherapy treatment in paediatric oncology patients.     

Conscious sedation with remifentanil and midazolam during brief painful procedures in children.

OBJECTIVE: To test the hypothesis that remifentanil, because of its favorable pharmacokinetic properties, would be advantageous to use in combination with midazolam to provide analgesia and sedation during brief painful procedures. DESIGN: Prospective observation and data collection. SETTING: University hospital. PATIENTS: Seventeen children aged 2 to 12 years, who underwent 20 brief, painful procedures. INTERVENTIONS: Administration of intravenous midazolam hydrochloride, 0.05 mg/kg, and remifentanil hydrochloride, 1 microg/kg, followed by a remifentanil infusion at 0.1 microg x kg(-1) x min(-1). The dose was titrated at 5-minute intervals to levels of sedation and analgesia. MAIN OUTCOME MEASURES: Successful remifentanil doses, times to discharge readiness, side effects, complications, and requirement for additional medications. RESULTS: The technique was successful in 17 of 20 procedures. The mean +/- SD successful dose was 0.4 +/- 0.2 microg x kg(-1) x min(-1). Four children developed hypoxemia that abated with mild stimulation; 1 child became unresponsive and required positive-pressure ventilation. The mean +/- SD time to reach discharge criteria was 9.5 +/- 4.3 minutes. Hypoxemia was avoided in 10 of 13 patients by continuous stimulation throughout the procedure. CONCLUSION: The use of remifentanil and midazolam during brief, painful procedures results in rapid times to discharge but is complicated by a high incidence of life-threatening respiratory depression at subtherapeutic levels.     

Efficacy and safety of rectal thiopental, intramuscular cocktail and rectal midazolam for sedation in children undergoing neuroimaging

BACKGROUND: This study was designed to investigate the overall usefulness of rectal thiopental, rectal midazolam and i.m. modified cocktail (meperidine-chlorpromazine hydrochloride-feniramin maleat) in 70 children undergoing computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: The dosage of thiopental was 50 mg per kg for infants under 6 months of age, 35 mg per kg between six and 12 months, and 25 mg per kg for older children. The maximal dose did not exceed 700 mg in this study. The dosage of midazolam was 1 mg per kg for all children. A modified cocktail was described as a formulation including 11 mg/mL of meperidine, 2.8 mg/mL of chlorpromazine and 2.8 mg/mL of pheniramine maleat. The dosage of modified cocktail was 0.1 mL per kg for all children. RESULTS: The mean induction time for the i.m. cocktail was significantly longer than that for rectal thiopental (P < 0.001). The mean duration of deep sedation was 60.79 +/- 27.00 min with rectal thiopental and 58.74 +/- 39.70 min with i.m. cocktail (P > 0.05). Although the mean duration of sleep for rectal thiopental and i.m. cocktail was similar, the mean discharge duration for i.m. cocktail was significantly longer than that for rectal thiopental (P < 0.05). Children sedated with the cocktail therapy also required a longer period of observation in the department. Significant decreases in heart rate, systolic blood pressure and oxygen saturation occurred in three groups (P < 0.001). Significant decreases in body temperature occurred after rectal thiopental and i.m. cocktail therapy (P < 0.01). The effect of rectal midazolam was minimal. CONCLUSIONS: Rectal thiopental may be the drug of choice for pediatric sedation because it has a more rapid onset and offset of action. It is also safe and effective at the dosage studied in children undergoing MRI. Rectal midazolam also may be used in children undergoing CT imaging because of minimal side-effects.