Brief Reports

Indian Pediatrics 1999;36: 1023-1028

Painless Invasive Procedures

From the Departments of Pediatrics, Command Hospital, Bangalore 560 007, India and *Department of Pediatrics, B.J. Medical College, Pune, India.
Reprint requests: Group Captain T.S. Raghu Raman, Professor and Head, Department of Pediatrics, Command Hospital (Air Force), Bangalore 560 007, India.
Manuscript received: July 22, 1998;
Initial review completed: September 7, 1998;
Revision accepted: April 22, 1999

Pediatric patients seldom need medication for the relief of pain. They tolerate discomfort well(1). There is widespread ignorance about pain and its refief in childhood. Too many children suffer from pain as a result of medical attitudes to pain reflief, which lead to inadequate and ineffective therapy. It is true even today that most of the Pediatric centers do not practice any form of sedation procedures and if so there is no uniformity(2). There has been an increase in invasive diagnostic, radiologic, and minor surgical procedures on pediatric patients outside the traditional operating room setting. Sedation during such procedures is inadequate and unscientific. Every child has the fear of needle and injection. Hence a procedure which starts with a painful intervention is bound to result in heightened anxiety and non-cooperation. Ketamine as a sedative has been in use for short procedures in the operating room. It is an excellent analgesic and amnesic agent. Traditionally it has been used parenterally. A few studies have used injection ketamine orally for sedation in children undergoing painful procedures(3,4). However there is no consensus about the dose of ketamine to be administered. The present study was done to establish the efficacy of injection ketamine administered orally as a sedative in children undergoing painful invasive procedures and to determine the adequate dosage of ketamine.

Subjects and Methods

This was a prospective hospital based study conducted from April 1996 to March 1997. Peer review and consent from ethical committee was taken. Prior to procedure, written consent from parent of the child was obtained. Parents were also encouraged to stay during the procedure. The inclusion criteria were children above the age of one year undergoing lumbar puncture, bone marrow aspiration and biopsy, liver biopsy and kidney biopsy. The exclusion criteria were (i) Acutely ill children with unstable cardio-respiratory status and (ii) Children with hypertension, intracranial space occupying lesions and raised intracranial pressure.

Children entering the study were serially indentified. The identified child was kept nil orally for six hours prior to the procedure. Baseline vital parameters, namely, blood pressure and respiratory rate were recorded. Injection ketamine was given orally diluted in 0.3 ml/kg of 25% dextrose in a dosage ranging from 6 to 10 mg/kg. The first 25 cases were given a dose of 6 mg/kg, the second 25 cases were given 8 mg/kg and the last 25 cases were given 10 mg/kg. Vital parameters were monitored continuously till the end of procedure. The sedation level and recovery assessment was made on parameters given in Table I.

Table I^__Sedation Level and Recovery Assessment.

During the procedure the children were not restrained and response was observed and recorded. After the procedure was completed, every child was monitored for the next two hours to assess recovery and any emergence phenomenon. During and after the procedure, resuscitation kit (ambu bag, laryngoscope, endotracheal tube, suction catheters, oxygen source and emergency drugs) were kept ready. Children having pharyngeal hypersecretion were managed with frequent observation and oropharyngeal suction. Children who were not sedated with the administered dose of ketamine were not subjected to the selected invasive procedure. They were posted for procedure at a later date.

The observations were analyzed for: (a) Efficacy and side effects of orally administered ketamine in the three dosage groups; and (b) Recovery time in the three groups. The statistical analyses included in the present study were: (a) Efficacy and side effects of orally administered ketamine in the three groups was assessed by chi-square test for equality of more than two proportions; and (b) Recovery time was assessed by applying Chi-square test for testing the hypothesis that two criteria of classification are independent when applied to same set of data.

Results

Total of seventy-five children were included in the present study and divided into 3 equal groups based on the dosage of ketamine_Group A (6 mg/kg), Group B (8 mg/kg) and Group C (10 mg/kg). The age and sex distribution of the cases is shown in Table II.

Table II^__Age and Sex Distribution (n = 75).

M_Male; F_Female.

The type of proce-dures done in the three groups were lumbar puncture (n=27), bone marrow aspiration (n=24), bone marrow biopsy (n=13), liver biopsy (n=10) and kidney biopsy (n=1). In group A 10 out of 25 children had adequate response to the administered dosage of keta-mine and the procedure could be completed. Similar figures for groups B and C were 19 out of 25 and 22 out of 25. The difference in proportion of response was statistically significant (p <0.05). In other words children given 10 mg/kg of ketamine showed no resistance as compared to children on either 6 or 8 mg/kg of ketamine. The distribution of recovery time in relation to drug dosage is reflected in Table III.

Table III^__Distribution of Recovery Time in Relation to Ketamine Dosage.

The recovery time was independent of administered dosage of ketamine (p >0.05).

The analysis suggested that recovery time is independent of dosage of ketamine.

The side effects noted in the present study in the three groups are highlighted in Table IV.

Table IV^__Side Effects (n = 75).

  None of the differences between the groups were significant (p >0.05).

There was no significant difference between the three groups in respect of side effects (p >0.05). The emergence phenomenon noted in six children were only moderate in the form of agitation and restlessness; none required any drug therapy. Children with hypersecretions (n=15) remained capable of clearing the airway and responding appropriately throughout the procedure. Three children had transient and mild increase in systolic blood pressure, returning to normal without any medication. Other than this, there were no other cardiovas-cular abnormalities. Based on vital parameters and clinical observations, there were no cases in whom hypoxia occurred clinically. Pulse oximetry was not used during the procedure.

Discussion

The problem of adequate sedation and pain refief in children undergoing painful and invasive procedures has remained a subject of continuing debate starting from a period when pain relief in children was ignored to the present when discussion is being held to determine as to what is ideal sedation. Children recognize and miss their parents, are capable of perceiving  painful injection, recovery from the sedation is quick and with minimal side effects. Presence of parents in such a situation would lend more to the acceptance of the procedure.

In the pediatric anesthesiology literature, many medications have been studied as premedicants to decrease secretions, prevent anxiety or to provide analgesia and sedation(5). Two such medications, which have been reviewed recently are orally administered ketamine and midazolam(5,6). Ketamine is a derivative of phencyclidine, which binds to opiate receptors producing a state of deep sedation. Although an excellent analgesic and amnestic agent, it also results in a number of undesirable side effects like production of copious secretions, increase in heart rate, blood pressure and intracranial pressure. Analgesia following ketamine administration outlasts the period of anesthesia and this effect occurred even at subanesthetic doses of ketamine(7). This drug may be administered intravenously, orally and rectally. Route of administration and the duration and depth of desired sedation determine the dose of Ketamine. In low doses, 0.5 to 1.0 mg/kg intravenous, the child will be lightly sedated for a very brief period (fewer than 10 minutes); 5 - 10 mg/kg (intravenous or intramuscular) will produce a deeply sedated child sufficient to allow insertion of an intravenous catheter, but this dose will also will produce a state of general anesthesia. Ketamine has been administered orally and rectally (6 to 10 mg/kg) with excellent sedation(8). Admi-nistered orally, it has a very high hepatic first pass effect with only 16% of the dose being bioavailable. Time to maximum sedation is approximately 20 to 25 minutes with patients blinking, staring, losing their lid reflexes, demonstrating nystagmus and appearing dissociated. Grant et al.(9) studied the pharmacokinetics and analgesic effects of IM and oral ketamine in six healthy adult threatening situations, such as being placed in the procedure table, but lack the ability to comprehend explanations and accept reassurance. An unpremeditated child, upon being separated from his or her parents often becomes frantic and difficult to manage regardless of whether a general or local anesthetic is planned. The child's trauma heightens parental anxiety as well. All of these events make for an uncomfortable experience for the parent and child, which may lead to poor compliance with further required procedures. A struggling and crying child, number of assistants, flurry of activity, raising anxiety in the doctor undertaking the procedures and anxious parents just outside the door is a very familiar scene for pediatricians. Added to this is the negative result of the procedure. Hence an ideal premedication should be one that gives adequate sedation and analgesia, avoids any  volunteers. Pain thresholds were increased at 15 minutes and 30 minutes after IM injection and at 30 minutes after oral ketamine. The plasma ketamine concentration associated with analgesia was 150 ng/ml following the IM dose, but only 40 ng/ml after the oral dose. Oral administration was, however, associated with much greater concentrations of the metabolite norketamine, which may have contributed to the analgesic effect. The authors define a mean plasma concentration of 150 ng/ml associated with analgesia following IM injection. They also conclude that IM injection avoids the very high peak concentrations produced by IV injection, which may be associated with hypertension and emergence phenomenon. Oral ketamine (6 mg/kg) also has been compared to meperidine (2 mg/kg) and promethazine (0.5 mg/kg). The efficacy of the ketamine sedation was reportedly greater, with shorter onset and postoperative recovery times (10). The clinical characteristics of two oral premedicants was compared in 40 healthy children scheduled for ambulatory dental surgery(5). The dose of ketamine used in this study was 5.0 mg/kg. Both drugs were found equally effective in sedating the children within 20 minutes. However 20% of children in ketamine group became tearful on separation from their parents. No side effects were observed(5). In another study(11), the superiority of oral ketamine as an analgesic and sedative for wound care procedures in Pediatric patients with burns was studied using for the first time oral suspension of the drug in a dose of 10 mg/kg.

The psychic disturbances following ketamine vary in incidence from less than 5% (in children) to greater than 30% (in adults). Reported disturbances include alteration in mood state and body image, dissociative experiences, floating sensations, vivid dreams or illusions and occasionally delirium. In children, side effects of excess salivation, purposeless movements unrelated to surgical stimuli, emergence reactions, and, rarely, prolonged behavioral changes have been reported after intravenous and intramuscular administration(12). Gutstein et al.(6) in a similar study of oral ketamine as preanesthetic medication using 3 mg and 6 mg per kg, observed increased secretions in 13 to 33%, nystagmus in 7 to 20%, vomiting in 13 o 20% and crying in 8 7% cases. Administering atropine before the procedure can prevent excessive secretions, the most significant side effect. The route of administration could be oral or intramuscular. Oral atropine imparts a bitter taste and time to peak decrease in salivation is 2 hours, significantly slower than the time to peak ketamine effect (20 minutes). Intramus-cular route defeats the very purpose of avoiding any injection before the selected procedure. The results of the study by Gutstein et al. indicate that atropine pretreatment is unnecessary.

Few factual points emerge from the above references. Oral ketamine has been used in minor procedures only. Secondly the dosage of ketamine has not been uniform but arbitrary. Thirdly there is no pharmacokinetic study in children using ketamine in oral and IM route. The objective of the present study was to determine the most ideal dose for a child undergoing invasive diagnostic/therapeutic procedure. It was found that oral ketamine in a dose of 10 mg/kg gives the ideal combination of good sedation with minimal emergence phenomenon. The side effects such as nystagmus, hypersecretions and transient hypertension were seen in almost equal number of patients in the different groups. Hyper-secretion can be easily managed with proper airway precaution only and avoiding atropine as a premedication. The analysis also suggested that the recovery time was independent of the dosage of ketamine. This observation requires to be studied in a larger sample size. The recommendations of the Committee on drugs and guidelines for monitoring children given sedation are very relevant. One of the specific guideline given is that children undergoing conscious sedation shall have continuous quantitative monitoring of oxygen saturation (e.g., pulse oximetry) and heart rate, and intermittent recording of respiratory rate and blood pressure. These should be monitored and recorded in a time based record(13). The study is limited by the fact that pulse oximetry was not used during the procedure to document any oxygen saturation. However no child based on vital parameters and other clinical signs demonstrated any gross respiratory insuffi-ciency. This small pilot study enables us to draw the following conclusions: (a) Injection Keta-mine given orally in a sweetened mixture in a dosage of 10 mg/kg provides adequate conscious sedation in children undergoing invasive procedures; (b) Side effects noted were hypersecretions, transient hypertension, nystag-mus and emergence phenomenon, none of which required any active interventions; (c) To provide for safe sedation in children undergoing invasive procedures using ketamine in a dosage of 10 mg/kg, there is need to monitor with pulse oximetry and reasonably conclude that there is no oxygen desaturation.

References

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10. Petros AJ. Oral ketamine - its use for mentally retarded adults requiring day care dental treatment. Anesthesia 1991; 13: 646-647.

11. Yvonne Humphries RN, Michelle Melson RN, Gore D. Superiority of oral ketamine as an analgesic and sedative for wound care procedures in the Pediatric patient with burns. J Burn Care Rehabil 1997; 18: 34-36.

12. Holister GP, Burn JMB. Side effects of ketamine in pediatric anesthesia. Anesth Analg 1974; 53: 264-267.

13. Committee on Drugs. Guidelines for monitoring and management of Pediatric patients during and after sedation for diagnostic and therapeutic procedures. Pediatrics 1992; 89: 1110-1115.