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PEDIATRIC ANESTHESIA

Perioperative Complications in Children with Pulmonary Hypertension Undergoing Noncardiac Surgery or Cardiac Catheterization

Mario J. Carmosino, MD^*, Robert H. Friesen, MD^*, Aimee Doran, CPNP, and Dunbar D. Ivy, MD

From the Departments of *Anesthesiology; and Pediatrics (Cardiology), The Children’s Hospital and University of Colorado School of Medicine, Denver, Colorado.

Address correspondence and reprint requests to R. H. Friesen, MD, Department of Anesthesiology, The Children’s Hospital, 1056 E. 19th Ave., Denver, CO 80218. Address e-mail to friesen.robert{at}tchden.org.

	Abstract

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BACKGROUND: Pulmonary arterial hypertension (PAH) can lead to significant cardiac dysfunction and is considered to be associated with an increased risk of perioperative cardiovascular complications.

METHODS: We reviewed the medical records of children with PAH who underwent anesthesia or sedation for noncardiac surgical procedures or cardiac catheterizations from 1999 to 2004. The incidence, type, and associated factors of complications occurring intraoperatively through 48 h postoperatively were examined.

RESULTS: Two hundred fifty-six procedures were performed in 156 patients (median age 4.0 yr). PAH etiology was 56% idiopathic (primary), 21% congenital heart disease, 14% chronic lung disease, 4% chronic airway obstruction, and 4% chronic liver disease. Baseline pulmonary artery pressure was subsystemic in 68% patients, systemic in 19%, and suprasystemic in 13%. The anesthetic techniques were 22% sedation, 58% general inhaled, 20% general IV. Minor complications occurred in eight patients (5.1% of patients, 3.1% of procedures). Major complications, including cardiac arrest and pulmonary hypertensive crisis, occurred in seven patients during cardiac catheterization procedures (4.5% of patients, 5.0% of cardiac catheterization procedures, 2.7% of all procedures). There were two deaths associated with pulmonary hypertensive crisis (1.3% of patients, 0.8% of procedures). Baseline suprasystemic PAH was a significant predictor of major complications by multivariate logistic regression analysis (OR = 8.1, P = 0.02). Complications were not significantly associated with age, etiology of PAH, type of anesthetic, or airway management.

CONCLUSION: Children with suprasystemic PAH have a significant risk of major perioperative complications, including cardiac arrest and pulmonary hypertensive crisis.

	Introduction

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Pulmonary arterial hypertension (PAH) is defined as the presence of a mean pulmonary artery pressure (PAP) that exceeds 25 mm Hg at rest or 30 mm Hg during exercise. PAH can be idiopathic (primary) or associated with a variety of underlying causes (1–3). Patients with PAH are generally considered to be at greater risk for the development of life-threatening perioperative cardiovascular complications. Increases in pulmonary vascular resistance (PVR) will increase right ventricular afterload, and can lead to right ventricular dysfunction. A potentially fatal complication is a pulmonary hypertensive crisis, characterized by a rapid increase in PVR to the point where PAP exceeds systemic blood pressure (BP). The resulting right heart failure leads to a decrease in pulmonary blood flow, decreased cardiac output, hypoxia, and biventricular failure (4). Other perioperative mechanisms associated with right-sided heart failure in patients with PAH include hypovolemia (inadequate preload), right ventricular dilation (compression of the left ventricle), systemic hypotension (decreased coronary perfusion), and hypoxemia. The pathophysiology of PAH, treatment options, and anesthetic considerations have been recently reviewed (1–3). The purpose of this study was to describe the incidence of perioperative complications and associated factors in children with PAH undergoing noncardiac surgery or cardiac catheterization.

	METHODS

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Data Collection
This retrospective cohort study was approved by the Colorado Multiple IRB. The database of the Pulmonary Hypertension Program at The Children’s Hospital was used to identify patients who underwent general anesthesia or sedation from the years 1999 through 2004. Most patients were enrolled in an IRB-approved protocol, "PEACH: A prospective evaluation of adolescents and children with pulmonary arterial hypertension," and all were referred to the Pulmonary Hypertension Program after initial diagnosis of PAH by echocardiogram. Cardiac surgical procedures were excluded. The medical record was reviewed and specific variables from the perioperative record were noted: age, gender, operation or procedure performed, diagnoses and etiology of PAH, the type of anesthetic administered (sedation, general inhaled, total IV anesthesia (TIVA)), anesthetic airway management, vital signs preoperatively and during the procedure, including systemic BP, pulse oximetry (Spo₂), capnography (Petco₂), and cardiac catheterization data when available, including measurements of PAP and PVR. Baseline PAP was defined as the initial PAP measured during cardiac catheterization, before any intentional pharmacologic or ventilatory manipulations of PVR. For noncardiac catheterization procedures, baseline PAP was obtained from the most recent cardiac catheterization or estimated from the preoperative echocardiogram. Severity of baseline PAH was classified as subsystemic (PAP <70% of systemic BP), systemic (PAP = 70%–100% of systemic BP), and suprasystemic (PAP >100% of systemic BP) based on mean pressures.

Evidence for incidents and complications occurring intraoperatively through 48 h postoperatively was sought from the anesthetic record, postanesthetic flowsheets, surgical notes, and progress notes. An incident was defined as an observed change in monitored values that was transient, had no effect on the patient’s condition, and required minimal or no treatment. A minor complication was defined as a transient event that had no long-term ill effect on the patient and resolved with specific treatment. A major complication was defined as a potentially life-threatening event requiring immediate treatment (5). If a complication was noted, pertinent historical details and laboratory data were recorded.

Anesthetic and Sedation Management
Preoperative assessment in all patients included a recent physical examination by a pediatric cardiologist, a recent electrocardiogram and echocardiogram, and review of the latest cardiac catheterization data. Close communication between the Pulmonary Hypertension Team and anesthesiologist was made in all cases. Inhaled nitric oxide (iNO) was readily available for all procedures.

General anesthesia was administered by pediatric anesthesiologists experienced in cardiac anesthesia. As many anesthetics exhibit mixed hemodynamic effects, and may be unacceptable when used in full anesthetic dosage, we used a balanced anesthetic technique in which subanesthetic doses of several drugs were combined to provide general anesthesia. Oral or IV midazolam was administered for preanesthetic sedation. Induction was cautiously achieved with midazolam, fentanyl, and a small dose of propofol or low concentration of sevoflurane. Inhaled anesthesia was maintained with isoflurane or sevoflurane; TIVA was maintained with infusion of propofol and either intermittent fentanyl or continuous remifentanil. Rocuronium or pancuronium was used for neuromuscular blockade as indicated. We used tracheal intubation in most patients, but used the laryngeal mask airway or facemask when appropriate for the procedure. Infiltration of local anesthetic by the operator at the surgical site helped the anesthesiologist to avoid high doses of general anesthetics.

Sedation was administered by a pediatric cardiologist to selected patients having cardiac catheterizations. Midazolam and fentanyl (rarely meperidine) was the most commonly used combination, and the airway was unaided.

Postoperatively, patients who exhibited signs of right heart failure, were unstable, or were beginning IV epoprostenol therapy were admitted to the pediatric intensive care unit. Stable patients requiring observation, such as those being weaned from intraoperative iNO or beginning oral sildenafil, were admitted to the cardiac ward for overnight observation. Asymptomatic, stable patients who were not changing therapy were discharged after brief procedures.

Statistical Analysis
Statistical analyses were performed using JMP 6 software (SAS, Cary, NC). Patient and procedural characteristics and the incidences of complications and of changes in vital signs were subjected to descriptive statistics. ² analysis was used to compare the incidences of complications among types of procedure, types of anesthetic, methods of airway management, age, etiologies of PAH, and baseline PAP. To assess the association of each nominal variable with the outcome, major complication, bivariate contingency tables were created. Logistic regression analysis was performed to assess the association between each continuous variable and the outcome, major complication. Variables with P < 0.20 in the univariate analysis, as well as clinically relevant variables, were then subjected to multivariate logistic regression analysis to determine the individual impact of the variables on the outcome, major complication.

	RESULTS

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Of 196 patients in the PAH database, 156 patients (Table 1) underwent 256 procedures (Table 2). The most frequent procedure was cardiac catheterization (55%), of which 68% were associated with intentional manipulations of PVR (e.g., hypoxic or hyperoxic challenge and iNO) to investigate the severity of PAH. Central venous access was most frequently performed to provide a port for IV treatment of PAH. Airway procedures included tonsillectomy, adenoidectomy, bronchoscopy, and tracheostomy. Abdominal procedures included gastric fundoplication, open liver biopsy, gastrostomy, cholecystectomy, bowel resection, and splenectomy. Thoracic procedures included open lung biopsy, anterior spinal fusion, and epicardial pacemaker insertion. Other procedures included imaging, dental, posterior spinal fusion, gastrointestinal endoscopy, and myringotomy. Anesthetic techniques and airway management are summarized in Table 2.

Incidents
Clinically significant decreases in Spo₂ (Spo₂ <90% in noncyanotic patients or an absolute decrease >5% in cyanotic patients) occurred during 21% of the procedures. Of these 44% accompanied intentional manipulations of Fio₂ for diagnostic purposes during cardiac catheterization. Clinically significant increases in Petco₂ or Paco₂ (>45 mm Hg) were observed during 22% of the procedures; these were not significantly more frequent during laparoscopic procedures (n = 9, P = 0.11). Clinically significant decreases in systemic BP (>20% from baseline) were observed in 20% of procedures. Clinically significant increases in PAP (>20% from baseline) occurred during 19% of cardiac catheterization procedures (PAP was not measured during other procedures). The frequency of incidents was not significantly associated with type of procedure, type of anesthetic, method of airway management, etiology of PAH, or severity of baseline PAP.

Minor Complications
Bradycardia responding to treatment with IV atropine occurred in two patients, and supraventricular tachycardia requiring IV adenosine occurred in one patient, all during cardiac catheterization. These were thought to be stimulated by intracardiac manipulation of the catheter. Hypotension associated with remifentanil infusion occurred during cardiac catheterization in a 16-yr-old patient with systemic PAH associated with chronic airway obstruction; the hypotension resolved after discontinuation of the remifentanil.

Two patients had transient decreases of Spo₂ in the postanesthesia care unit that responded immediately to oxygen administration. One was a 3-yr-old child with systemic PAH and history of lung hypoplasia and diaphragmatic hernia who had undergone closure of tracheostomy under inhaled anesthesia with an endotracheal tube. The other was a 30-yr-old patient with suprasystemic PAH associated with Eisenmenger’s syndrome and trisomy 21 who had undergone dental extractions under TIVA with an endotracheal tube.

Two patients required unplanned postoperative mechanical ventilation for respiratory issues. One was a 6-mo-old infant with suprasystemic PAH associated with lung hypoplasia who had undergone cardiac catheterization under TIVA with an endotracheal tube. The other was a 5-mo-old infant with subsystemic PAH associated with bronchopulmonary dysplasia and prematurity who had undergone laparoscopic Nissen fundoplication under inhaled anesthesia.

The frequency of minor complications was not significantly associated with type of procedure, type of anesthetic, method of airway management, etiology of PAH, or severity of baseline PAP.

Major Complications
Cardiac arrest not associated with pulmonary hypertensive crisis occurred in a 9-mo-old infant with subsystemic PAH undergoing device closure of a ventricular septal defect. Resuscitation with external cardiac massage and IV epinephrine was successful within 90 s; there were no sequelae.

Pulmonary hypertensive crisis (defined as an increase in PAP to exceed systemic BP, a decrease in systemic BP, and a decrease in Spo₂) occurred in six patients during cardiac catheterization procedures (3.8% of patients, 4.3% of cardiac catheterization procedures, 2.3% of all procedures). Pulmonary hypertensive crises in two patients resolved with specific treatment intraoperatively. Two patients required postoperative mechanical ventilation and intensive care unit support for 24–48 h before the pulmonary hypertensive crises and hemodynamic instability completely resolved. Two patients with baseline suprasystemic PAH had intractable pulmonary hypertensive crises resulting in postoperative death (1.3% of patients, 1.4% of cardiac catheterization procedures, 0.8% of all procedures). Details of the pulmonary hypertensive crisis patients are summarized in Table 3.

Major complications were significantly more frequent in patients with baseline suprasystemic PAH (P = 0.014) (Fig. 1), but were not significantly associated with type of anesthetic, method of airway management, or etiology of PAH. All major complications occurred during cardiac catheterization procedures. Death occurred significantly more frequently in patients with baseline suprasystemic PAH (P = 0.015).

View larger version (23K): [in this window] [in a new window]   Figure 1. The frequency of major complications was significantly associated with the severity of baseline pulmonary artery hypertension (PAH) (P = 0.014 by 2 analysis).

Variables that were significantly associated with major complications by univariate analyses were severity of baseline PAH, duration of procedure, and a clinically significant intraoperative decrease in Spo₂ (Table 4). The multivariate predictor of major complications was suprasystemic baseline PAH (Table 5).

	DISCUSSION

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Our data demonstrate that children with PAH have a significant risk of major perioperative cardiovascular complications, including cardiac arrest, pulmonary hypertensive crisis, and death, when undergoing sedation or anesthesia for cardiac catheterization procedures. Overall complications were more frequent in children with systemic or suprasystemic PAH, but were not associated with patient age, etiology of PAH, type of anesthetic, or airway management techniques.

The incidence of perioperative cardiac arrest that we found to be associated with PAH is much greater than published incidences of perioperative cardiac arrest in all children. The initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) Registry report an overall incidence of perioperative cardiac arrest of 0.0265%, an incidence of anesthesia-related cardiac arrest of 0.014%, and an incidence of anesthesia- related death of 0.0036% (6). The overall incidences of perioperative cardiac arrest and death in a pediatric teaching hospital without open cardiac or neurosurgical services were reported to be 0.033% and 0.004%, respectively (7). Our institution’s unpublished overall incidence of perioperative cardiac arrest from 2001 through 2004 was 0.024% (Quality Assurance Program, Department of Anesthesiology, The Children’s Hospital, Denver). In comparison, the three cardiac arrests that occurred during our 256 procedures in children with PAH represent an incidence of 1.17%, and the two deaths 0.78%.

Major complications are more frequent in association with pediatric cardiac catheterization. A leading pediatric cardiac center reported the incidences of perianesthetic cardiac arrest and death associated with cardiac catheterization to be 0.49% and 0.08%, respectively (5). Our institution’s incidence of intraoperative cardiac arrest and perioperative death associated with cardiac catheterization (excluding PAH patients) from 2000 through 2004 was 0.07% and 0.11%, respectively (Quality Assurance Program, Division of Cardiology, The Children’s Hospital, Denver). In comparison, the three cardiac arrests that occurred during our 141 catheterization procedures in children with PAH represent an incidence of 2.1%, and the two deaths 1.4%.

There is not a significant body of literature about PAH and its associated complications in children who require anesthesia care. Studies of adults demonstrate that the presence of PAH significantly contributes to adverse outcomes after both cardiac and noncardiac surgery (8,9). Reich et al. (8), in a retrospective analysis of computerized intraoperative databases, determined that pulmonary hypertension was a predictor of perioperative myocardial infarction and death in a large cohort of adult patients undergoing coronary artery bypass grafting. Ramakrishna et al. (9) performed a retrospective analysis of adult patients with PAH who had undergone noncardiac surgery and reported a high incidence of early postoperative morbidity and a mortality rate of 7%, indicating the serious impact of PAH. In a retrospective study of 276 pediatric and adult patients with congenital heart disease undergoing noncardiac surgery, Warner et al. (10) found that PAH, cyanosis, congestive heart failure, and age <2 yr was a predictor of perioperative morbidity.

Studies of adults with PAH have reported other perioperative factors that have varying importance in predicting morbidity. Long duration of anesthesia was a significant independent predictor of morbidity in adults with PAH (9). Although long duration of the procedure achieved significance in our univariate analysis, it did not prove to be an independent predictor of major complications when subjected to multivariate logistic regression (long duration was due to the time taken to resuscitate and/or stabilize children with PAH crises before transfer to the pediatric intensive care unit). Similar to the findings of Warner et al. (10), our data suggest that general anesthesia versus nongeneral anesthesia is not a significant factor associated with complications.

Compared to the published studies of PAH in adults, ours is limited by a relatively small number of subjects; thus, our ability to identify a significant association between some variables and complications may have been limited by inadequate power, or a Type II statistical error. A further limitation of retrospective studies is that details of clinical management and other data can be incomplete or lacking; thus, some complications or other important information can be missed. We anticipate that both outcomes and contributing factors such as anesthetic management and surgical techniques will be more precisely defined as experience grows.

Several mechanisms can be associated with hemodynamic deterioration in patients with PAH. Of critical importance among these mechanisms is a rapid increase in PVR related to pulmonary arterial vasoreactivity. Hypercarbia, hypoxia, acidosis, and noxious stimuli such as pain and airway instrumentation can trigger a rapid increase in PVR (1,11–14) that can lead to a pulmonary hypertensive crisis and/or right heart failure. It was not apparent during this retrospective review that hypercarbia, acidosis, pain, or airway instrumentation contributed to any complications; Spo₂, Petco₂, and arterial blood gases were generally well documented. However, one pulmonary hypertensive crisis that responded quickly to iNO appeared to be associated with exposure to subambient Fio₂ during evaluation of pulmonary vasoreactivity. Unrecorded noxious stimuli, including catheter stimulation of the heart or pulmonary vasculature, could have contributed.

Anesthesiologists should be aware that other mechanisms can also contribute to right-sided heart failure in patients with PAH. Hypovolemia can provide inadequate preload to the right ventricle, leading to decreased stroke volume, cardiac output, and pulmonary blood flow. Systemic hypotension or a decrease in systemic vascular resistance can cause a decrease in coronary artery blood flow, leading to biventricular ischemia. Compensatory right ventricular hypertrophy or dilation can compress the septal wall of the left ventricle, leading to inadequate filling of the left ventricle, decreased stroke volume, and decreased cardiac output. Hypoxemia related to problems with ventilation, lung disease, or decreased pulmonary blood flow can further impair ventricular function.

The hemodynamic and pulmonary vascular effects of anesthetic drugs have been reviewed elsewhere (2,15–20) and should be considered in the anesthetic care of children with PAH. Sedation without general anesthesia is a common technique for cardiac catheterization of selected patients and was used in 56 of the 141 cardiac catheterization procedures in this series. Fentanyl and midazolam were the most commonly used combination and are thought to have little direct effect on the pulmonary vasculature. Oversedation does occur during procedural sedation, however (21), and can be associated with hypercarbia, hypoxemia, and airway obstruction in patients managed with a natural airway and spontaneous ventilation (22). These clinical problems can also occur during general anesthesia and must be avoided in patients with PAH.

Selective pulmonary vasodilators are frequently used perioperatively, even in the absence of hemodynamic deterioration. During cardiac catheterization procedures for evaluation of PAH, iNO is administered to test pulmonary vasoreactivity. For other surgical procedures, iNO is usually administered prophylactically intraoperatively and continued postoperatively via nasal cannulae (23). Postoperative withdrawal of iNO or other pulmonary vasodilators can be associated with life-threatening rebound pulmonary hypertension; this must be anticipated and can be attenuated by administration of other pulmonary vasodilators (24,25). Treatment of pulmonary hypertensive episodes involves 100% oxygen, hyperventilation, attenuation of noxious stimuli, and pharmacologic pulmonary vasodilators. Such treatment and drugs have been reviewed elsewhere (1–3).

In summary, our data indicate that children with suprasystemic PAH have a perioperative risk of major complications, including cardiac arrest, pulmonary hypertensive crisis, and death that is many times greater than that reported for the general pediatric population. It is important that anesthesiologists be aware of this increased risk, understand the pathophysiology of PAH, form an appropriate anesthetic management plan, and be prepared to treat cardiovascular deterioration.

	ACKNOWLEDGMENTS

 
The authors thank Jane Gralla, PhD, and Zhaoxing Pan, PhD, for their assistance with statistical analysis.

	Footnotes

 
Accepted for publication November 29, 2006.

Supported by the General Clinical Research Center branch of the National Center for Research Resources, National Institutes of Health Grant M01-RR00069.

Presented in part at the meeting of the Society for Pediatric Anesthesia and American Academy of Pediatrics Section on Anesthesiology, Ft. Myers, FL, February, 2006.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Carmosino, M. J. Articles by Ivy, D. D. Search for Related Content PubMed PubMed Citation Articles by Carmosino, M. J. Articles by Ivy, D. D. Related Collections Cardiovascular Complications Monitoring (Cardiac) Pediatrics