Sedation with intravenous ketamine and midazolam for painful procedures in children

BACKGROUND: Children often require relief of pain and anxiety when undergoing painful procedures. The purpose of this study is to evaluate the effectiveness and safety of painful pediatric procedures performed by pediatric intensivist, using the combination of intravenous ketamine and midazolam for sedation and analgesia. METHODS: The records of the patients who received intravenous ketamine-midazolam combination for painful procedures in the pediatric sedation unit of a university hospital over a 3 year period were retrospectively reviewed to determine indications, dosing, assessment of the level of sedation, adverse events, and recovery time for each procedural sedation and analgesia. RESULTS: A total of 227 children aged 4 months to 18 years were admitted to the pediatric sedation unit for a total of 356 procedures. The indications for procedural sedation and analgesia included bone marrow aspiration or biopsy (50.8%), central venous catheter insertion (27%), and others (22%). A total of 46 adverse events (12.9%) were observed. These adverse events included SpO2 below 85% without apnea (n = 14), apnea (n = 3), transient stridor (n = 2), hypertension and tachycardia (n = 8), hypersalivation (n = 6), vomiting (n = 5), hallucinatory emergence reaction (n = 4), and rash (n = 4). There were no adverse outcomes attributable to ketamine and midazolam combination. CONCLUSION: Skilled pediatric intensivists can safely and effectively administer ketamine and midazolam to facilitate painful procedures outside the operating room setting.     

The use of intravenous gamma-globulin for prevention of sepsis in pre-term infants. A controlled clinical trial

This paper reports a randomized clinical trial to study the effect of an intravenous gamma-globulin preparation to prevent sepsis in pre-term newborn infants. 80 infants were enrolled: 37 of birthweight less than or equal to 1500 g and 43 of birthweight 1501-2000 g. In each group 20 infants received an intravenous preparation of gamma-globulin (0.5 g/kg/wk); the remaining 17 and 20, respectively, served as control cases. No significant differences in the occurrence of sepsis were observed between the group receiving prophylactively intravenous gamma-globulin and the control group. This is particularly evident in infants under intensive care (35% of the total population): in this group 2/3 of sepsis occurred in infants who received IgG. Among the infants with sepsis, the presence of an umbilical artery catheterization represented a significant risk-factor. The post-dose increment of serum IgG did not differ significantly in infants with and without sepsis; the post-dose serum disappearance rate in concentration appears identical in the two groups.     

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.     

早产儿静脉营养疗效及并发症观察

目的 探讨早产儿静脉营养(PN)的疗效及安全性.方法 将不能耐受全胃肠道喂养的早产儿60例(胎龄28～36周,体重1 00～2 450 g),于生后24～72 h输注氨基酸及脂肪乳;同时根据病情尽早经口微量喂养.并于生后第1天与第7大检测肝功能、胆红素、甘油三酯、总胆固醇及尿素氮,每天临测体重、微量血糖.结果 生理性体重下降持续时间为(6.60±1.26)d,PN结束时58例体重均增加,平均每日增加(21.5±5.14)g.治愈率96.7%(58/60),病死率3.3%(2/60).肠外营养相关性胆汁淤积(PNAC)发生率为3_3%,PN 周后血总胆汁酸(TBA)升高35例,与PN的比较,差异有统计学意义(P<0.001);PN前后患儿血红蛋白、血小板、转氨酶、胆固醇、甘油三酯、尿素氮、钠离子、钾离子、钙离子均在正常范围内.结论 早产儿PN能促进生长发育,体重增长快,提高早产儿治愈率;PN可引起PNAC,胆汁酸增高可作为PNAC的早期生化指标.     

Comparison of a morphine and midazolam combination with morphine alone for paediatric displaced fractures: a randomized study

Aim: To compare the efficacy of sublingual midazolam with oral morphine versus that of oral morphine with placebo in a paediatric population attending an emergency department (ED) with acute long‐bone fractures. Methods: A sample of children aged 5–16 years with clinically deformed closed long‐bone fractures was randomized to groups receiving either oral morphine (0.5 mg/kg)/sublingual placebo or oral morphine (0.5 mg/kg)/sublingual midazolam (0.2 mg/kg). The main exclusion criteria were narcotic or benzodiazepine use, significant head injury, multiple organ failure, femoral fracture and allergy. Pain scores were rated on a 100‐mm visual analogue scale (VAS) at 0, 15, 30, 60, 90 and 120 min. Results: Fifty‐eight children were enrolled (mean age: 10.5 years, SD 2.7). Fractures concerned the radius or ulna in 43 cases (74.1%), the humerus (22.4%) and the tibia or fibula (3.5%). No significant difference in VAS scores was observed between the two treatment arms (p = 0.72). Drowsiness was significantly more frequent in the midazolam group (p = 0.007) during the first 2 h after administration. No serious adverse event was observed. Conclusion: The analgesic performances of morphine and the combination of morphine with midazolam assessed by VAS were similar in children presenting at the ED with a long‐bone fracture.     

Long-term outcome for endoscopic third ventriculostomy alone or in combination with choroid plexus cauterization for congenital aqueductal stenosis in African infants

Object The authors have previously reported on the overall improved efficacy of endoscopic third ventriculostomy (ETV) combined with choroid plexus cauterization (CPC) for infants younger than 1 year of age. In the present study they specifically examined the long-term efficacy of ETV with or without CPC in 35 infants with congenital aqueduct stenosis treated at CURE Children's Hospital of Uganda during the years 2001-2006. Methods Infants with congenital aqueductal stenosis were treated during 2 distinct treatment epochs: all underwent ETV alone, and subsequently all underwent ETV-CPC. Prospectively collected data in the clinical database were reviewed for all infants with an age < 1 year who had been treated for hydrocephalus due to congenital aqueductal stenosis. Study exclusion criteria included: 1) a history or findings on imaging or at the time of ventriculoscopy that suggested a possible infectious cause of the hydrocephalus, including scarred choroid plexus; 2) an open aqueduct or an aqueduct obstructed by a membrane or cyst rather than by stenosis; 3) severe malformations of the cerebral hemispheres including hydranencephaly, significant segments of undeveloped brain, or schizencephaly; 4) myelomeningocele, encephalocele, Dandy-Walker complex, or tumor; or 5) previous shunt insertion. The time to treatment failure was analyzed using the Kaplan-Meier method to construct survival curves. Log-rank (Mantel-Cox) and Gehan-Breslow-Wilcoxon tests were used to determine whether differences between the 2 treatment groups were significant. Results Thirty-five patients met the study criteria. Endoscopic third ventriculostomy alone was performed in 12 patients (mean age 4.7 months), and combined ETV-CPC was performed in 23 patients (mean age 3.5 months). For patients without treatment failure, the mean and median follow-ups were, respectively, 51.6 and 48.0 months in the ETV group and 31.2 and 26.4 months in the ETV-CPC group. Treatment was successful in 48.6% of the patients who underwent ETV alone, as accurately predicted by the Endoscopic Third Ventriculostomy Success Score (ETVSS), and in 81.9% of the patients who underwent ETV-CPC (p = 0.0119, log-rank test; p = 0.0041, Gehan-Breslow-Wilcoxon test; HR 6.42 [95% CI 1.51-27.36]). Conclusions Combined ETV-CPC is significantly superior to ETV alone for infants younger than 1 year of age with congenital aqueductal stenosis. The fact that the outcome for ETV alone was accurately predicted by the ETVSS suggests that these results are applicable in developed countries.     

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.     

Synergistic sedation with oral midazolam as a premedication and intravenous propofol versus intravenous propofol alone in upper gastrointestinal endoscopies in children: a prospective, randomized study

OBJECTIVES: The primary objective of the present study was to compare the required dose of intravenous (IV) propofol between group A (synergistic sedation with an oral dose of midazolam combined with IV propofol) and group B (IV propofol alone), in diagnostic upper gastrointestinal endoscopy (UGIE) in pediatric patients. The secondary objective was to compare the safety, the efficacy, the ease of IV line placement and the ease of separation from parents between the 2 groups. METHODS: Fifty-four consecutive children (aged 3 y or older) who underwent UGIE were randomly assigned to 1 of the 2 medication regimens. Patients in group A (n = 26, mean age: 8.1 y) received midazolam (0.5 mg/kg) orally. Thirty minutes after the midazolam dose was given, repeated IV doses of propofol 0.5 mg/kg were administered titrated to achieve the level of deep sedation. Patients in group B (n = 28, mean age: 9 y) received IV propofol alone with the same methodology and sedation end point. RESULTS: The mean dose (1.8 +/- 0.7 mg/kg) of propofol administered in group A patients was remarkably lower compared with that (2.9 +/- 0.9 mg/kg) of group B. Multivariate stepwise logistic regression analysis revealed that among sex, age, ASA grade and the type of sedation, the synergistic sedation was the only factor associated with the ease of IV line placement (chi(2) = 16.3, P < 0.001) and the ease of separation from parents (chi(2) = 41.6, P < 0.001). Additional multivariate stepwise logistic regression analysis revealed that among sex, age, ASA grade and the type of sedation, synergistic sedation was the only factor associated with a higher level of patient comfort (chi(2) = 35.5, P < 0.001). The recovery time was significantly shorter in group B patients (7.7 +/- 3.6 min) compared with that of group A (25.9 +/- 4.1 minutes) (P < 0.01). The 2 regimens were equally safe. CONCLUSIONS: Our data suggest that synergistic sedation with an oral dose of midazolam combined with propofol may benefit the children who undergo UGIE with regard to lower mean dose of propofol used, easier IV line placement, easier separation from the parents, less pain induced by the IV line placement and greater patient comfort.     

Dose of intravenous lipids and rate of bacterial clearance in preterm infants with blood stream infections

Background  

Intravenous lipid emulsion (IVLE) is an integral part of the total parenteral nutrition (TPN) regimen in neonates. The use of IVLE during sepsis is the subject of controversy because it may interfere with phagocytosis of microbes by macrophages and may lead to significant hypertriglyceridemia.     

The use of recombinant tissue plasminogen activator in the management of infective intracardiac thrombi in pre-term infants with thrombocytopaenia

Bacterial endocarditis complicated by the development of intra-cardiac thrombus presents a difficult management dilemma in the pre-term infant. Here we present our experience with three infants who had this condition, all of whom were successfully managed using therapy with recombinant tissue plasminogen activator (r-TPA). Therapy in one of the infants was particularly instructive, as the condition was further complicated by severe thrombocytopaenia, making the decision to treat using r-TPA difficult.     

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.     

The treatment of nocturnal enuresis. A comparative study between desmopressin and acupuncture used alone or in combination]

During the period from March to September 1989, 40 children suffering from primary nocturnal enuresis, aged between 5 and 14 years, were included in a study to assess the comparative therapeutical efficacy of DDAVP and acupuncture. Children were divided into four groups of 10: group A was treated with DDAVP, group B was treated with acupuncture, group C was treated with DDAVP and acupuncture and group D was treated with placebo (control). The trial design included 3 periods: observation (2 weeks), treatment (8 weeks) and follow-up (4 weeks). Nineteen children completed the study. The efficacy of treatment, which was expressed as a percentage of dry nights, was high in both the DDAVP and acupuncture groups, when used separately. The combined treatment of DDAVP and acupuncture appeared to be the most efficacious both in terms of the percentage of dry nights at the end of treatment and in relation to the stability of results, even after the end of the study. The paper gives a detailed analysis of correlations between type of treatment and urinary osmolarity.     

The effects of treatment with growth hormone alone or in combination with oxandrolone in a group of Turner's syndrome children. A preliminary study

The authors analyzed the clinical and psychological effects of GH (group 1) and GH plus oxandrolone (group 2) in a group of 11 Turner girls aged 6.3-14 years. The results showed a significant improvement of posttreatment height velocity vs pretreatment height velocity for both study groups. No significant differences were found between the two groups. A girl of group 2 manifested a defect of sexual identification.     

静脉注射阿托品治疗先天性肥厚性幽门狭窄

目的探讨静脉注射阿托品治疗先天性肥厚性幽门狭窄症的方法及疗效.方法应用静脉注射阿托品疗法治疗先天性肥厚性幽门狭窄症25例.静脉注射阿托品开始剂量为0.04mg/(kg·d),每日增加0.01 mg/kg至显效.呕吐停止后阿托品改为口服,两周后停药.结果24例于用药后10 d内呕吐停止,显效时阿托品剂量在0.04～0.14 mg/(kg·d)之间.停药后无呕吐复发者.住院时间10～18 d.1例无效经手术治愈.结论静脉注射阿托品疗法治疗先天性肥厚性幽门狭窄症疗效满意,具有无创、并发症少等优点.     

静脉注射阿托品治疗先天性肥厚性幽门狭窄

目的探讨静脉注射阿托品治疗先天性肥厚性幽门狭窄症的方法及疗效。方法应用静脉注射阿托品疗法治疗先天性肥厚性幽门狭窄症25例。静脉注射阿托品开始剂量为0．04 mg/(kg·d),每日增加0．01 mg/kg至显效。呕吐停止后阿托品改为口服,两周后停药。结果 24 例于用药后10 d内呕吐停止,显效时阿托品剂量在0．04-0．14 mg/(kg·d)之间。停药后无呕吐复发者。住院时间10-18 d。1例无效经手术治愈。结论静脉注射阿托品疗法治疗先天性肥厚性幽门狭窄症疗效满意,具有无创、并发症少等优点。