Abstract
Objective
Premature infants are more prone to cardiorespiratory complications after surgery than term infants. Risk factors for postoperative apnea include post-conception age, gestational age, postnatal age, birth weight, history of respiratory distress syndrome, bronchopulmonary dysplasia, anemia, necrotizing enterocolitis, use of opioids or nondepolarizing muscle relaxants, aminophylline use, history of apnea, body weight at operation, and pre-existing disease. The aim of this study was to identify the most important factors associated with postoperative extubation and respiratory outcomes among premature infants undergoing cryotherapy for retinopathy of prematurity (ROP).
Methods
We retrospectively analyzed the clinical records of 62 premature infants, with mean ± standard deviation gestational age of 26.4 ± 2.3 weeks, birth weight of 914.8 ± 208.5 g, postconception age of 37.0 ± 2.8 weeks, and body weight at the time of operation of 1970.0 ± 446.8 g, who underwent cryotherapy for ROP.
Results
Only 17 infants were successfully extubated within 2 hours after operation. The most predictive factor for successful or unsuccessful extubation was body weight at the time of operation.
Conclusion
Body weight at the time of operation was the most important factor associated with postoperative ventilatory support among premature infants under-going cryotherapy for ROP.
Keywords
anesthesia; apnea; cryotherapy; premature birth; retinopathy of prematurity;
1. Introduction
Cryotherapy is an established surgical procedure to treat threshold retinopathy of prematurity (ROP) to prevent its progression to visual impairment and blindness.1 Clinically significant systemic complications, including apnea and bradycardia, may occur during and after therapy for ROP.2
Premature infants undergoing cryotherapy for ROP under topical anesthesia alone have more severe and protracted cardiorespiratory complications compared with those given general anesthesia via intubation.1,3,4 The risk factors for postoperative apnea have been widely studied and include gestational age (GA), postconception age (PCA), postnatal age (PA), birth weight, preanesthetic weight, history of necrotizing enterocolitis, bronchopulmonary dysplasia, respiratory distress syndrome (RDS), neonatal apnea, ongoing apnea, anemia, influence of anesthetic drugs, and effects of intermediate or long-acting muscle relaxants.3,5 The incidence of apnea is strongly associated with PCA and GA5 and the most significant risk factor was reported to be PCA.5−7 A GA of < 25 weeks has also been considered as an important risk factor.8 However, we believe that GA < 25 weeks may not be an important risk factor because respiratory muscle function and central nervous system continue to develop after birth. These earlier studies included premature infants (with varying PCA) undergoing various operations or the same operation by different surgeons. Only one study included premature patients who underwent therapy for ROP by the same operator, but the sample size was small, only 25 patients.8
Therefore, in this study, we retrospectively reviewed the medical records, including preoperative variables and anesthesia interventions, in 62 premature infants with PCA < 41 weeks and weight at time of operation < 2500 g, who underwent cryotherapy for ROP by the same surgeon. The aim of this study was to identify the most important factors associated with postoperative extubation and respiratory outcomes among premature infants with young PCA.
2. Methods
We retrospectively reviewed the clinical and operative records of 62 premature infants who were nursed during their neonatal period in the intensive care unit (ICU) and underwent cryotherapy for threshold retinopathy at Chang Gung Memorial Hos pital in Kaohsiung, Taiwan between January 1999 and January 2006. None of the patients had airway obstruction, hypocarbia, hypercarbia, neuromuscular blockade, narcotic overdose, temperature abnormalities,dehydration, anemia, electrolyte (calcium, magnesium, phosphorus) imbalance, hypoglycemia, aspiration, sepsis, pulmonary hemorrhage, intracranial hemorrhage, or seizure.8 The inclusion criteria were as follows: PCA < 41 weeks, weight at the time of operation < 2500 g, the procedure was the first operation to be done under general anesthesia, and the patient was not intubated or on mechanical ventilation 7 days before the operation.8 No premedication was used in our routine anesthetic management. Anesthesia was induced using standard procedures with 0.01 mg/kg atropine and 2−4 mg/kg ketamine (or 3−4 mg/kg propofol), and tracheal intubation was facilitated by administering 0.5 mg/kg atracurium. After tracheal intubation, anesthesia was maintained by 2% sevoflurane (end-tidal concentration) and N2O in oxygen at a flow rate of 2 L/min (N2O: O2= 1.3:0.7 L). We maintained an optimal depth of anesthesia by monitoring hemodynamic stability (< 20% of the baseline preanesthetic state) and adjusting the concentration of inhalation anesthetic (sevoflurane) throughout surgery. Opioids were not used during the operation.
We recorded GA, PCA, birth weight, preanesthetic weight, American Society of Anesthesiologists physical status, prenatal condition, perinatal medical history, Clinical Risk Index for Babies score (Table 1),9 duration of anesthesia, anesthetic drugs administered, fluids administered, body temperature, Cardiorespiratory Stability (CS) score (Table 2),4 postoperative complications, and indications for postanesthetic ventilatory assistance.3 We also reviewed intraoperative monitoring items, including heart rate, noninvasive arterial pressure, pulse oximetry, oropharyngeal temperature, inspired O2 and end-tidal CO2. Patients who received additional treatments during the operation, such as Xylocaine for bronchospasm, were excluded. Apnea was defined as cessation of breathing lasting > 20 seconds or < 20 seconds in combination with bradycardia, cyanosis or pallor.10
Neuromuscular blockade was routinely reversed with 0.05 mg/kg neostigmine and 0.02 mg/kg atropine. The infants were extubated if Bett’s signs (signs that the infant could be safely extubated, such as flexing the hip and knees to hold the feet off the bed)11 and if other parameters were present, including normal airway protective reflexes, alert mental status, hemodynamic stability, adequate arterial oxygen saturation with inspired oxygen fraction < 0.4, and maximum inspiratory pressure 90%, heart rate > 120 beats/min) or if prolonged apnea occurred (> 15 seconds).
2.1. Statistical analysis
Patients were divided into two groups according to postoperative outcome. The extubation group comprised patients who were successfully extubated within 2 hours after the operation. The ventilatory support group comprised patients who could not be extubated within 2 hours after the operation and needed continuous ventilatory care, including T-piece or ventilator use. Parametric data are expressed as means with standard deviation and categorical data are presented as numbers. Comparisons between the two groups were conducted using independent t tests or χ2 tests. Statistical significance was defined as p< 0.05. Logistic regression analyses were used to calculate univariate crude odds ratios (ORs) with 95% confidence intervals (CIs) with extubation as the outcome factor. Stepwise model selection with entry and stay criteria (p< 0.1) was used to estimate adjusted ORs with 95% CIs for significant risk factors associated with extubation in premature infants after ROP. All statistical analyses were conducted using SPSS version 13 (SPSS Inc., Chicago, IL, USA).
3. Results
We retrospectively reviewed the records of 62 premature infants who underwent cryotherapy for threshold ROP. The mean ± standard deviation GA was 26.4 ± 2.3 weeks and birth weight was 914.8 ± 208.5 g. At operation, the mean PCA was 37.0 ± 2.8 weeks and body weight was 1970.0 ± 446.8 g.
Forty-nine infants had a history of intubation and mechanical ventilation after birth. Apgar scores at 1 and 5 minutes were 3.8 ± 1.9 and 6.2 ± 1.4, respectively. The mean Clinical Risk Index for Babies score was 8.0 ± 4.0 (Table 3). Forty-nine infants had episodes of dyspnea and received surfactant therapy. No patient required O2 via a nasal cannula, endotracheal intubation, or mechanical ventilation before operation.
Tracheal extubation in the operating room was successfully performed within 2 hours after the operation in 15 infants. The remaining 47 infants did not meet the criteria for tracheal extubation and required mechanical ventilation in the neonatal ICU.
Table 3 summarizes the preoperative variables in both groups. There were no significant differences in sex, medical history, American Society of Anesthesiologists physical status, anesthetic procedure, or drugs administered during anesthesia between the two groups. However, there were statistically significant differences in GA (p= 0.04), intubation at birth (p= 0.034), PCA (p= 0.012), body weight at operation (p< 0.001) and CS scores (against baseline) on postoperative day 1 (p= 0.007).
Table 4 shows the ORs for several potential risk factors for postoperative extubation among premature infants undergoing cryotherapy for ROP.2 In univariate analyses, GA, intubation at birth, PCA and body weight at operation were significantly associated with postoperative extubation. After stepwise model selection, body weight at operation (OR = 0.996; 95% CI = 0.992−0.999; p= 0.016) and intubation at birth (OR = 0.093; 95% CI = 0.011− 0.821; p= 0.033) remained statistically significantly associated with postoperative extubation.
4. Discussion
Infants requiring treatment for ROP are extremely vulnerable to complications because the prevalence of ROP is highest among premature babies with very low body weight.4 Some studies have shown that premature infants undergoing cryotherapy for ROP under topical anesthesia alone develop more severe cardiorespiratory complications.4 Thus, endotracheal general anesthesia is preferable and controlled ventilation without end-expiratory pressure is used. In addition, unexpected deterioration during surgery may be avoided and the systemic hemodynamic instability is less protracted following cryotherapy under endotracheal general anesthesia.1,4
Patients who receive general anesthesia are even more stable than those who receive local anesthesia. However, postoperative monitoring in an ICU is necessary for at least 48 hours and the mean length of postoperative ventilation can be 22 hours.1 Postoperative apneic episodes in premature infants are attributed to immaturity of the respiratory system and immature brain stem functions.12,13 Tashiro et al developed a scoring system to predict the need for tracheal intubation after surgery.8 They found that the degree of prematurity at birth had greater effects on postoperative outcome compared with postnatal development. Furthermore, GA < 25 weeks was the most important risk factor for postoperative ventilatory support.8 In another study, Liu et al examined the validity and incidence of postanesthetic apneic episodes in infants and found that the PCA was < 41 weeks for all infants who required postoperative respiratory support.3
In a study of 20 infants with a median GA of 29 weeks who were initially ventilated for RDS, Dimitriou et al found that infants who were not successfully extubated had lower functional reserve capacity (FRC).14
In a related study, Poets et al determined the FRC in 14 preterm infants.15 In that study, FRC was measured at birth and at PCA of 33−40 weeks. The mean FRC values corrected for body weight were 22.9 mL/kg for O2 and 23.4 mL/kg for heliox.15 Meanwhile, Schmalisch and Wauer found a linear relationship between FRC and body weight in newborn infants.16 Vilstrup et al measured FRC at 2−4 cmH2O positive end-expiratory pressure in 15 neonatal infants with body weight 700−1950 g, and also found that FRC increased with body weight.17 Thus, body weight seems to be an important factor associated with FRC in premature infants.
RDS is the most common respiratory disorder in preterm infants and chronic respiratory morbidity is common after premature birth. Patients with bronchopulmonary dysplasia often develop severe respiratory failure in the neonatal period with chronic pulmonary fibrosis and airway smooth muscle hypertrophy. These patients also have reduced alveolar development and show poor lung function lasting up to 1 year after birth.18 Thus, lung injury may be directly related to the duration of invasive ventilation via the endotracheal tube.19 In our study, 80% of infants (49/62) had a history of dyspnea and needed intubation at birth. Thus, postoperative development of apnea and respiratory outcomes seem to be due to poor lung function in these infants.
Eighty-five percent of our patients receiving muscle relaxants needed postoperative respiratory support. We postulate that the residual paralytic effect of the muscle relaxant is due to the low resistant muscle fibers, which are less able to eliminate the drug. Although anesthetic drugs are known to affect the ventilatory control mechanism, differences in the anesthetic management of the patients here were not associated with the postanesthesia respiratory outcomes. A similar conclusion was reached by Liu et al.3
The CS score was recorded as an improvement, worsening, or no change versus baseline, and takes into account the requirement for controlled ventilation. In the present study, the mean length of postoperative ventilation in patients with unsuccessful extubation within 2 hours was 30 hours. This might explain why there was a significant difference in the CS score on postanesthetic day 1.
Several studies have examined factors associated with respiratory outcomes in premature infants. However, most of those studies only include cases under ventilatory support in ICUs, or cases undergoing miscellaneous operations, such as inguinal hernia repair and ventricular peritoneal shunt.7,20,21 Although Woodhead et al reported 45 infants undergoing ROP laser surgery, using a nasal prong for anesthetic management,22 few studies have described anesthetic management for a single specific procedure, such as cryotherapy for ROP. Based on the current literature, we cannot yet make any firm recommendations in terms of the optimal management of premature neonates with extremely low body weight undergoing laser therapy for ROP. Clearly, further controlled studies are required. Compared with the earlier studies, we found that body weight at operation was the most significant factor predicting postoperative intubation after cryotherapy for ROP in premature infants. In contrast, PCA and GA were not significantly associated with postoperative intubation.
In summary, we retrospectively reviewed the clinical records of 62 patients undergoing transscleral cryotherapy for progressive ROP. The PCA of all patients was < 41 weeks and their body weight at the time of operation was < 2500 g. We found that body weight at operation, but not GA or PCA, was the most important risk factor for prolonged postoperative intubation in premature infants after cryotherapy for ROP. Therefore, the postoperative care team should pay particularly close attention to premature infants with low body weight at operation, because they may need longer postanesthetic respiratory support to avoid hypoxemia after extubation.