Proceduralist Given Sedation is Safe and Feasible in Pediatric Flexible Bronchoscopy

Abstract

The objective of this research was to study the effectiveness and safety of proceduralist given sedation in pediatric flexible bronchoscopy. Flexible bronchoscopy was performed in all 267 patients. All patients received midazolam and/or ketamine. The median (interquartile range [IQR]) age of the studied population was 16 (18) months. The indication of bronchoscopy varied. The mean ± standard deviation (SD) dose of midazolam was 0.109 (0.03) mg/kg and that of ketamine was 1.17 (0.43) mg/kg. We observed minor side effects of procedural sedation. All patients underwent procedure successfully. Flexible bronchoscopy in children can be safely performed under sedation using a combination of midazolam and ketamine.

Introduction

Flexible bronchoscopy (FB) is one of the important tools in the evaluation and management of pediatric respiratory disorders. ¹ Over the last decade, its utility has markedly expanded due to high-quality optics and advent of a range of accessories. It provides detailed anatomical and functional information of upper and lower airways. Many therapeutic interventions such as the removal of foreign bodies, placement of stents, balloon dilatation of stenotic segments, intrabronchial instillation of glue, and removal of mucus plugs are now routinely being done with the help of flexible bronchoscopy in the pediatric population. ^{2 3} Whereas in adult bronchoscopy, sedation has a controversial role, ⁴ its usefulness in children is well accepted. ^{5 6} The aim of sedation is to facilitate the safe and successful performance of the procedure, as well as to minimize complications, and decrease the pain and anxiety associated with the said procedure. ⁷ Historically, procedural sedation and analgesia in children have been the domain of anesthesiologists; however, there is mounting evidence suggesting that procedural sedation and analgesia can also be safely provided by a nonanaesthesiologist. ⁸ The most commonly used agent is midazolam alone or in combination with opioid/ketamine/propofol. ^{1 9} Combination of midazolam with opioid or propofol is highly effective; however, sedation may be prolonged and respiratory depression may occur. Because of its favorable respiratory profile, ketamine may avoid some of these problems and recently many studies reported its safe and effective use in pediatric fiberoptic bronchoscopy, ¹⁰ but it has the disadvantage of causing increased salivation and secretions and resulting in emergence delirium, the latter is reduced with the coadministration of midazolam. ¹¹

The Department of Pediatrics at Sher-I-Kashmir Institute of Medical Sciences (SKIMS) is the only center in whole Kashmir valley where Pediatric flexible bronchoscopy facility is available. We perform all flexible bronchoscopies under sedation. It is given by bronchoscopy team without the presence of anesthesiologists. The aim of this project is to study the advantage and safety of proceduralist given sedation and analgesia in pediatric flexible bronchoscopy in resource-constrained settings.

This study aimed to find the utility of procedural sedation for flexible bronchoscopy in children and safety of proceduralist given sedation in pediatric flexible bronchoscopy using ketamine and midazolam combination.

Methods

This was a 3-year prospective observational study from January 2015 to December 2017 conducted in the department of pediatrics of a tertiary care hospital of Northern India. Prospective data of 267 patients, who underwent flexible diagnostic and/or therapeutic bronchoscopy, were analyzed. Children who were on a ventilator and/or intubated were excluded from the study. Written informed consent was taken from all patients or parents before undertaking the procedure. Majority of bronchoscopies were performed transnasally. The transoral route was used in nine patients. The authors used Olympus BF-XP160F (Olympus Medical Systems Corp., Japan) bronchoscope with channel size 1.2 mm in children less than 3 years of age and Olympus BF-MP-160F scope with a channel diameter of 2 mm, in children above 3 years of age. All procedures were performed in a bronchoscopy suite which is in close proximity to pediatric intensive care unit (ICU). Bronchoscopy team comprised of two bronchoscopists, one pediatric resident, one bronchoscopy technologist, and one nurse. Electrocardiogram and pulse oximetry were recorded continuously during the procedure and automated noninvasive blood pressure was monitored every 3 to 5 minutes. Supplemental oxygen was given at 4 L/min via nasal cannula. Desaturation ≤90% was managed by increase in oxygen flow rate and the use of oxygen mask. Two percent lidocaine gel was used locally to anesthetize nasal mucosa and 1 mL aliquots of 2% lidocaine in 1:1 dilution with normal saline were instilled by the “spray-as-you-go” technique. Supplemental local anesthesia was given as per requirement. All patients received midazolam bolus at 0.1 mg/kg over 1 minute. In addition to midazolam bolus, the majority of our patients received intravenous (IV) ketamine bolus at 1 mg/kg over 2 minutes diluted in normal saline. Signs of pain or discomfort, agitation, persistent cough, and inadequate motor or verbal response to manipulation were considered indicators for insufficient sedation, leading to administration of additional doses of IV ketamine bolus at 1 mg/kg/dose. The maximum upper limit of ketamine received by any patient was not higher than 3 mg/kg. Patients, who received ketamine, were also given IV glycopyrrolate 5 µg/kg to reduce ketamine-induced increased respiratory secretions. All these drugs were administered by a bronchoscopy technologist and were based on the judgment of the bronchoscopist. A standardized data extraction form was used to obtain the demographic and clinical data including patient age, sex, weight, comorbidities, procedure indication, duration of the procedure (time from scope insertion to scope removal), total midazolam and ketamine dose, pulse rate, baseline and lowest blood pressure, oxygen saturation, and adverse events if any during and/or within 1 hour of the procedure. Adverse events were predefined and classified as minor or major. Minor adverse events were defined as periprocedural transient apnea, hypoxia (oxyhemoglobin saturation < 90% for > 30 seconds). A drop in systolic blood pressure less than 20% from the baseline was assessed as a minor complication. Major complications included apnea and/or laryngospasm which require endotracheal intubation and blood pressure (BP) fluctuation > 20% from the baseline.

Statistical analysis was performed using SPSS 20 (IBM; Armonk, United States). The normality of the data was checked by using the Shapiro–Wilk test. Parametric data are expressed as mean ± standard deviation (SD) and nonparametric test as median (interquartile range [IQR]). Categorical variables are presented as percentages. The study was cleared by the ethical committee.

Results

A total of 369 bronchoscopies were performed by a bronchoscopy team during this period. Out of these, 58 bronchoscopies were performed in intubated patients and were excluded from the study. Thirty-seven procedures were done without sedation mainly for upper airway evaluation. Parents of seven patients didn't give consent to be part of the study. So, a total of 267 patients were enrolled. The age ranged from the newborn period to 14 years. There were 151 male patients and 116 female patients. Patient characteristics are shown in Table 1 . Indications for bronchoscopy included nonresolving/recurrent pneumonia ( n  = 79), recurrent/persistent wheeze ( n  = 38), stridor ( n  = 36), suspected foreign inhalation ( n  = 31), broncho alveolar lavage (BAL) culture in cystic fibrosis patients ( n =27), flexible endoscopic evaluation of swallowing (FEES; n  = 18). Chronic cough ( n  = 13), suspected hydatid disease ( n  = 13), hemoptysis ( n  = 8), interstitial lung disease ( n  = 4). Sedation was achieved with midazolam alone ( n  = 14) or in combination with ketamine ( n  = 253). Ketamine was avoided in neonates due to potentially unfavorable safety profile in this population. The cumulative doses of each drug used are summarized in Table 2 . No formal sedation scoring was done in our study, the level of sedation was titrated to ensure minimal or no patient movement or response during the procedure. The median (IQR) duration of the procedure was 15 (11) minutes. There were two major complications, where one patient developed prolonged apnea and needed endotracheal intubation. The second patient developed hypertension with increase in BP > 20% from the baseline. Minor complications in the form of hypoxia, transient bradycardia, transient apnea (< 20 seconds), BP fluctuations < 20% from the baseline were noticed in 27 (10.1%) patients. Tachycardia was not included in this list as the majority of our patients received bolus dose (5 µg/kg) of glycopyrrolate before bronchoscopy procedure which is known to cause tachycardia. Table 3 summarizes complications attributed to sedation in the studied population. Prolonged apnea in one patient required endotracheal intubation as initial bag and mask ventilation was not successful. Endotracheal intubation was done by a senior resident of pediatric ICU, who is pediatric advanced life support (PALS) trained and is part of the bronchoscopy team. This patient required mechanical ventilation and was successfully extubated after 3 hours. One patient developed hypertension after IV ketamine with BP fluctuation more than 20%. The procedure was postponed in view of the above complication. The patient was monitored in pediatric ICU and hypertension improved spontaneously with an hour. Hypoxia was managed by increased oxygen flow rate and use of oxygen mask. Transient apnea needed tactile stimulation. No treatment was required for BP fluctuations as these were transient and resolved spontaneously. None of our patients developed laryngospasm or bronchospasm during bronchoscopy. All our patients who had preprocedure wheeze on auscultation received levosalbutamol nebulization prior to bronchoscopy.

Table 1. Patient characteristics of the studied population ( n  = 267) .

Variable	Results
Age (mo), median (IQR)	16 (18)
Weight (kg), median (IQR)	10 (7)
Duration of symptoms (d), median (IQR)	21 (12)
Initial BP, median (IQR)	88 (16)
BP during a procedure, median (IQR)	90 (16)
Procedure time (min), median (IQR)	15 (11)

Abbreviations: BP, blood pressure; IQR, interquartile range.

Table 2. Doses of drugs used.

Drug	Dose of drug
Midazolam (mg/kg), median (IQR)	0.109 (0.03)
Ketamine (mg/kg), median (IQR)	1.17 (0.43)
Glycopyrrolate (µg/kg), median (IQR)	5 (0.29)

Abbreviation: IQR, interquartile range.

Table 3. Complications attributed to procedural sedation.

Complications	Frequency (%)
Minor complications:  • Hypoxia  • Apnea  • Transient bradycardia  • Mild BP fluctuation (<20% from baseline)	16 (6) 5 (1.8) 3 (1.1) 3 (1.1)
Major complications  • Prolonged apnea  • BP fluctuation (>20% from baseline)	1 (0.37) 1 (0.37)

Abbreviation: BP, blood pressure.

Discussion

Flexible bronchoscopy has become the procedure of choice in a large spectrum of pediatric airway disorders. Over the past decade, the field of interventional pulmonology using flexible bronchoscope is rapidly expanding. ³ With more complex and longer procedures, procedural sedation and analgesia have taken a center stage in contemporary bronchology. ¹² Sedation reduces the state of consciousness, while analgesia brings down pain perception. In pediatrics, unlike adult patients, the aim of sedation is to control behavior and facilitate safe completion of the procedure. ⁷ The analysis of our results suggests that proceduralist given sedation with midazolam and ketamine combination is effective, feasible, and safe in controlled settings. We didn't specifically record sedation scores; however, the combination was titrated to ensure minimal or no patient movement or response during the procedure. This depth of sedation allowed us to carry out the procedure safely with minimum patient discomfort. The mean (IQR) dose of midazolam was 0.109 (0.03) mg/kg and ketamine was 1.17 (0.43) mg/kg and the doses were given in aliquots. Ketamine with or without midazolam by nonanaesthesiologists has been shown in several large series to be useful in the performance of pediatric procedures. ¹⁰ We observed an acceptable rate of side effects, such as oxygen desaturation, brief apnea, transient bradycardia, nausea. All these adverse events were brief and improved with minimal intervention. None of our patients developed bronchospasm during the procedure, possibly due to the use of ketamine, a known bronchodilator, and the use of levosalbutamol nebulization prior to bronchoscopy in patients with clinical evidence of bronchospasm. ¹³ Increased airway secretions followed ketamine bolus is a common adverse effect; this was managed by a prior loading dose of glycopyrrolate which blunts this response. We did not encounter any episode of emergence delirium post ketamine infusion in our series. It was possibly due to coadministration of midazolam which is known to counter above complication. ¹¹ The rate of minor complications was similar to previously reported studies. ^{8 10}

The scope of procedural sedation has expanded tremendously, and it is no longer a domain restricted to anesthesiology. Procedural sedation is now often used outside traditional operating rooms for different pediatric daycare procedures. ¹³ In our study, procedural sedation was given by bronchoscopy technologist under the guidance of bronchoscopist. Our findings suggest that procedural sedation can also successfully be administered by nonanesthesiologists trained in pediatric resuscitation. Studies from other parts of the world also suggest that sedation technique performed by nonanesthesiologists during bronchoscopy is safe and cost-effective. ^{1 8 14} The major side effect was observed in two of our patients and both patients recovered fully. One patient needed brief endotracheal intubation and mechanical ventilation and the second patient required ICU monitoring for a sudden rise in blood pressure (20% of baseline) which improved spontaneously within 1 hour. Both these patients underwent bronchoscopy successfully at a later date. One patient developed prolonged apnea which needed endotracheal intubation and the second patient developed hypertension. Both patients were successfully managed. The American Academy of Pediatrics (AAP) ¹⁵ has issued updated clinical guidelines on the monitoring and management of pediatric patients receiving sedation for procedures. It states that practitioners who administer moderate sedation need to have the skills to rescue a child with apnea, laryngospasm, and airway obstruction, and to perform successful bag/mask ventilation and endotracheal intubation if needed. Additionally, the skilled observer must be trained in PALS. Our team is PALS trained and is well versed with endotracheal intubation and resuscitation. Furthermore, we do all our procedures in an ICU setting with all resuscitation facilities readily available.

In India, where the majority of public hospitals face the dearth of anesthesiologists, and there is no guideline available about procedural sedation in children, sedation and analgesia administered by the proceduralist appears safe in ICU setting provided the team is optimally trained in resuscitation and endotracheal intubation or laryngeal mask airway placement.

Conclusion

Flexible bronchoscopy in children can be safely performed by using midazolam and ketamine combination. The combination causes adequate sedation and analgesia for successful completion of the procedure. Furthermore, in resource-constrained settings, it is safe to use above regimen by proceduralists provided the team is adequately trained in resuscitation and airway management.