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Anesth Analg 1999;89:328
© 1999 International Anesthesia Research Society

PEDIATRIC ANESTHESIA

Ventilatory Response to CO2 in Children with Obstructive Sleep Apnea from Adenotonsillar Hypertrophy

Susan G. Strauss, MD*,{dagger}, Anne M. Lynn, MD*,{dagger}, Susan L. Bratton, MD*,{dagger}, and Mary Kay Nespeca, RN, BSN{dagger}

*Department of Anesthesiology, University of Washington School of Medicine; and {dagger}Department of Anesthesia and Critical Care, Children’s Hospital and Medical Center, Seattle, Washington

Address correspondence to Susan G. Strauss, MD, Department of Anesthesia and Critical Care, Children’s Hospital and Medical Center, P.O. Box 5371, Seattle, WA 98105.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
We measured the ventilatory response to CO2 as an indicator of respiratory control dysfunction in children with obstructive sleep apnea (OSA) scheduled for adenotonsillectomy. Measurements were performed in unpremedicated children via an endotracheal tube under 0.4%–0.5% end-tidal halothane anesthesia. Mean ventilatory CO2 response slopes for 11 children with OSA requiring adenotonsillectomy (Group I) were compared with those for 14 children without OSA requiring adenotonsillectomy (Group II) and 15 children without OSA requiring nonairway surgery (Group III). The mean ventilatory slope corrected for body surface area for Groups I, II, and III were 539 ± 338, 828 ± 234, and 850 ± 380 mL · min-1 · mm Hg ETCO2-1 · m-2, respectively (P < 0.05, Group I versus Groups II and III). Historical data—including snoring, apneic episodes >10 s, daytime hypersomnolence, and nocturnal enuresis—defined those with OSA. Obesity occurred more frequently in patients with OSA and with depressed ventilatory responses (P < 0.001). Children with OSA from adenotonsillar hypertrophy have a diminished ventilatory response to CO2 stimulation, compared with those without OSA symptoms. The depressed response may account, in part, for the reported increased risk of perioperative respiratory complications in this population.

Implications: Children with obstructive sleep apnea undergoing adenotonsillar surgery are at risk of postoperative respiratory compromise. We found that patients with a clinical history suggesting obstructive sleep apnea have a diminished ventilatory response to CO2 rebreathing, compared with controls.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Over the past 20 yr, the approach to tonsil and adenoid surgery has become progressively more conservative, and the profile of the adenotonsillectomy patient population has changed. The percentage of adenotonsillar surgery performed for recurrent infection has declined, whereas obstructive symptomatology as an indication for surgery has increased (1,2). The most severe obstructive symptom, obstructive sleep apnea (OSA), is defined as repeated apneic episodes >=10 s during sleep in which cessation of airflow at the nose and mouth occurs in the presence of continued respiratory efforts (3,4). Increased perioperative morbidity in patients with OSA from adenotonsillar hypertrophy has been reported (5,6).

Patients with OSA undergoing adenotonsillectomy procedures are at risk of postoperative respiratory compromise. Clinical experience and experimental evidence suggest that sedation from anesthetics, including inhaled anesthetics and narcotics, can decrease the activity of the pharyngeal dilator muscles responsible for maintenance of upper airway muscle tone and patency (7–9). Altered ventilatory response to CO2 stimulation has been suggested as an explanation for the propensity toward postoperative respiratory compromise in patients with severe obstructive apnea (6).

Several studies have incompletely identified children at risk for these complications. McColley et al. (5) and Rosen et al. (10) retrospectively identified high-risk criteria for predicting postoperative respiratory compromise in patients with severe OSA as defined by polysomnography. Determining the severity of OSA, however, is a clinical challenge. Brouilette et al. (11) prospectively investigated whether the severity of OSA could be classified from a clinical scoring system based on three questions about breathing during sleep. In children with no OSA or severe OSA defined by polysomnography, the OSA score was an accurate predictive tool; however, there was a group of patients with "possible OSA" in whom the score was not useful.

The goal of our study was to determine whether children with upper airway obstruction from adenotonsillar hypertrophy, in whom a detailed clinical history suggested OSA, have an altered ventilatory response to CO2 and to assess whether any clinical or laboratory correlates may identify them preoperatively.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
After institutional review board committee approval and written consent from parents, history and physical examination data were obtained via a questionnaire. OSA was defined as all of the following: snoring, mouth breathing, restless sleep with frequent awakenings, apneic pauses >=10 s, and one or more secondary symptoms elicited from the questionnaire that included nocturnal enuresis (in children >=4 yr old), daytime hypersomnolence, swallowing difficulties, failure to thrive, behavioral problems (e.g., hyperactivity, aggression), difficulty in school, and developmental delay. The ventilatory response to CO2 was measured for ASA physical status I and II patients aged 2–10 yr scheduled for elective surgery after induction of anesthesia and endotracheal intubation. Individuals taking medications known to cause central nervous system depression (e.g., anticonvulsants, anxiolytics, narcotic analgesics) or stimulation (e.g., Ritalin [methylphenidate], theophylline) were excluded. Patients with mental retardation, severe craniofacial abnormalities, or neuromuscular diseases were also excluded.

Patients were divided into three groups: Group I (n = 11) contained patients scheduled for adenotonsillectomy with OSA symptoms as defined herein; Group II (n = 15) contained patients scheduled for adenotonsillectomy without OSA symptoms; and Group III (n = 14) contained patients scheduled for other ambulatory surgery without OSA symptoms. With IV cannulation, laboratory testing included hematocrit, serum bicarbonate, capillary blood gas, and baseline room air oximetry for Groups I and II and a 12-lead electrocardiogram for Group I. The surgeons assessed tonsillar size in Groups I and II by estimating relative oropharyngeal occlusion. Tonsillar size was rated on a scale of 1–4 (1 = <25% obstruction of the oropharynx, 2 = >25%–50%, 3 = >50%–75%, 4 = >80%).

Patients did not receive premedication. Anesthetic induction with nitrous oxide, oxygen, halothane, and IV atropine 10 µg/kg was followed by endotracheal intubation without neuromuscular blockade. The endotracheal tube was lubricated with 2% lidocaine ointment to minimize coughing during the CO2 response testing. The patient resumed spontaneous ventilation without nitrous oxide until the end-expiratory halothane was 0.5% for at least 2 min.

CO2 response testing was performed using a closed breathing circuit with a partially filled 15-L reservoir bag primed with 0.8% halothane, 95% oxygen, and 5% CO2. The circuit was connected to the patient’s endotracheal tube via a one-way valve, with an in-line heated pneumotachograph, an infrared capnometer, and an anesthetic gas analyzer. The pneumotachograph and capnometer were calibrated before each study. Data were collected during 3-min periods of rebreathing. In-line computer analysis of minute ventilation—integrated from the pneumotachograph flow signal, respiratory rate, and end-tidal CO2 read at 10-s intervals—was used to generate a CO2 response curve that was subjected to linear regression analysis. End-tidal CO2 increased at least 15 mm Hg or to a maximal end-tidal value of 70 mm Hg during rebreathing studies.

Before initiation of the study, a sample size of 13 patients per group was estimated by power analysis. Assumptions were based on previously published normal values for CO2 response slopes (12), with an expectation to detect a difference of 50%, given a power of 0.9 and an {alpha} of 0.05. Ventilatory response to CO2—the slope of the minute ventilation versus end-tidal CO2 measurements—was compared among groups by using a one-way analysis of variance, and the Tukey B test for post hoc pairwise comparisons. CO2 slopes were normalized with body surface area (BSA) values to adjust for patient age and size. Nominal data were analyzed and compared by using the {chi}2 test for trend. Fisher’s exact test was used when fewer than five patients were expected. P < 0.05 was considered significant. The Tukey B test was used for comparison of end-tidal halothane among the three groups.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Forty patients were enrolled in the study. The patient demographic profile is shown in Table 1. Responses to the questionnaire are shown in Table 2.


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  		Table 1. Demographics
 

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  		Table 2. Clinical Data
 
Group means and standard deviations (SD) of patients’ ventilatory response to CO2 slope were computed. Mean slopes and SD for Groups I, II, and III were 539 ± 338, 828 ± 234, and 850 ± 380 mL · min-1 · mm Hg ETCO2CO2-1 · m-2, respectively. Groups II and III were statistically different from Group I (Table 3). The mean end-tidal halothane concentrations were 0.47 ± 0.07, 0.55 ± 0.02, and 0.51 ± 0.01, respectively, for Groups I, II, and III (P = not significant).


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  		Table 3. Ventilatory Response Slope and Laboratory Data
 
No statistical differences were observed in hematocrit, serum bicarbonate, or preoperative SaO2 values among the three study groups. There also was no significant difference in tonsillar size between Group I and Group II. Furthermore, electrocardiograms in Group I did not show any abnormality, such as right ventricular hypertrophy. The definition of OSA in Group I, as detailed in Methods, was corroborated in review of the questionnaire, as shown in Table 2. Patients in Group I had a heavier body weight than those in Groups II or III (P < 0.05) (Table 1).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
We demonstrated that children with OSA symptoms from adenotonsillar hypertrophy have a diminished ventilatory response to CO2 rebreathing in the presence of halothane, compared with children without OSA symptoms undergoing adenotonsillar or nonairway surgery. Simple laboratory studies—such as hematocrit, serum bicarbonate measurements, and abnormalities on the electrocardiogram—were not useful in preoperatively identifying children with depressed CO2 responses. Obesity occurred more frequently in Group I than in Groups II and III.

To compare more accurately the ventilatory response to CO2 across a pediatric population, differences in patient size are considered when calculating the CO2 response slope (12,13). Most often, patient weight is factored into the CO2 response slope calculation to adjust for these differences (13,14). We chose to correct for size by incorporating BSA into the calculations because Group I patients weighed statistically more than patients in Groups II and III, and adjusting ventilatory response slopes with patient weight might create falsely low values for that group. We thought that using BSA in our calculations would better reflect the ventilatory response to CO2 rebreathing because BSA takes into account both height and weight and is a better representation of body habitus. If the ventilatory responses to CO2 rebreathing are adjusted for patient weight, then the values for Group I patients are significantly less than Groups II and III, as was found using BSA for size normalization.

Attempts to define quantitatively the "normal" hypercapnic ventilatory drive have been difficult. Hirshman et al. (15) found that the ventilatory response to CO2 rebreathing in adults was highly variable, making it difficult to characterize an individual as abnormal. A study by Lopata et al. (16) showed that, in the presence of flow-resistive loading, healthy adult men showed a diminished ventilatory response to CO2 chemostimulation. Results from a retrospective study by Ingram and Bishop (6) may synthesize information gleaned from Hirshman et al. (15) and Lopata et al.’s work (16). Compared with control subjects, Ingram and Bishop’s (6) data suggests that patients with a history of severe OSA (characterized by hypercapnia and cor pulmonale) from adenotonsillar hypertrophy have a diminished ventilatory response to CO2 two years after adenotonsillectomy and relief from upper airway obstruction. This diminished response was present in the absence of persistent hypercarbia (6). These findings suggest that patients with severe OSA may represent one extreme of a normal range of response to CO2 rebreathing.

Limitations of the present study should be considered. To reduce any differences in upper airway resistances among our patients, we measured the ventilatory response to CO2 while they were intubated under a light level of halothane anesthesia. We performed the ventilatory measurements while maintaining an end-tidal halothane concentration of 0.4%–0.5%, the minimal anesthetic level necessary to tolerate an endotracheal tube without coughing. Previous studies indicate that halothane produces a dose-dependent depression of the ventilatory response to CO2 in adults and children at halothane concentrations >0.3% and paradoxical breathing at concentrations >0.5% (13,14,17–19). The decreased mean slope in Group I may have been affected by the halothane concentration; however, the ventilatory measurements in all the study groups were performed with the same end-tidal halothane concentration. The decreased ventilatory response in Group I may represent a heightened sensitivity to the ventilatory depressant and paradoxical breathing effects of halothane, compared with the control groups. Whether the difference between Group I and Groups II and III would be present without halothane is unknown.

Our findings are consistent with those of Laurikainen et al. (20), who reported no correlation between tonsillar and/or adenoid tissue size and severity of OSA symptoms. It has been suggested that this discrepancy may be due to a dysfunctional neural control mechanism of the hypopharyngeal muscles that are responsible for maintaining airway patency, resulting in decreased pharyngeal size in patients with OSA (21,22). Differences in neuromuscular control and sensitivity to the neuromuscular effects of halothane may also help to explain why Group I patients—who were more likely to be mildly obese, compared with patients in Groups II and III—had a depressed ventilatory response. A study designed to compare the ventilatory response to CO2 in obese versus nonobese OSA patients or obese patients with and without OSA may clarify the role of obesity in OSA and ventilatory depression. Our study group was too small to allow this comparison.

Although we identified a group of patients with an altered ventilatory response to CO2 rebreathing, we did not encounter any perioperative complications—specifically, postoperative apneic episodes and oxygen desaturation. Although we did not control for differences in postoperative care, particularly the use of opioid analgesics for pain relief, patients in our study were not given sedative premedication that could potentiate respiratory depressant effects of opiates and residual subanesthetic doses of inhaled anesthetics that may persist into the immediate postoperative period (8,9,23). If coupled with the absence of a normal ventilatory response to hypoxia associated with halothane anesthesia (17), the depressed ventilatory responses in patients with OSA might increase the danger of postoperative hypoxic episodes. We did not see this in our small group of OSA patients. We also did not determine whether any particular anesthetic technique could offer greater postoperative benefits than an inhalation-based technique.

In conclusion, we demonstrated that children with a history of OSA from adenotonsillar hypertrophy have a depressed ventilatory response to CO2 stimulation under 0.4%–0.5% end-tidal halothane anesthesia, compared with children without OSA symptoms. Studies designed to isolate and compare the various components of the ventilatory process in patients with OSA with those of normal controls will help to elucidate where their ventilatory control processes may differ and how they are affected by anesthetics. Our clinical definition of OSA can be used to identify this patient population. Our results indicate that a clinical history with direct, specific questioning did identify a group of children with a depressed CO2 response. Drugs known to cause ventilatory depression (sedative hypnotics, anxiolytics, narcotics, inhaled anesthetics) must be prospectively evaluated for safety and efficacy in these patients.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication April 4, 1999.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press