Incremental Risk of Obstructive Sleep Apnea on Cardiac Surgical Outcomes

By Kaw, R; Golish, J; Ghamande, S; Burgess, R; Et al

Aim. Obstructive sleep apnea (OSA) is not generally acknowledged as a perioperative risk factor. High incidence of Sleep disordered breathing has been noticed in patients with cardiovascular disease. The Sleep Heart Health Research Study Group found Apnea-Hypopnea indices (AHI) as modest as 1-10 to be associated with cardiovascular disease manifestations. Given the lack of data we chose to study the incremental risk of OSA in patients undergoing cardiac surgery.

Methods. We looked at 25 587 patients who underwent cardiac surgery at the Cleveland Clinic. Of these, 37 patients were also identified on the Cleveland Clinic Sleep center database as having OSA. Each of these 37 cases were propensity matched for multiple covariates with 5 controls within a distance of 0.001 units. An assumption was made that if the surgery was performed within two years of the diagnosis of OSA, the patient had OSA at the time of the surgery.

Results. Higher incidence of encephalopathy (p=0.008), postoperative infection (0.028) and increased ICU length of stay (p=0.031) were noted in the group with OSA after cardiac surgery. The difference in the rates of infection was mostly accounted for by the presence of mediastinitis (8.1% vs 1.6%). Differences in the rates of reintubation, tube time, and overall postoperative morbidity were not statistically significant.

Conclusion. Increased risk for postoperative complications is suggested in patients with OSA undergoing cardiac surgery. This risk is underestimated on account of lack of awareness about the incidence of OSA in the general population and the cardiovascular population in particular, difficulties in clinical suspicion and diagnosis and limited use of polysomnography.

KEY WORDS: Obstructive sleep apnea – Heart – Surgery.

Obstructive sleep apnea (OSA) has many potential consequences, including increased risks of hypertension, cardiovascular events and cerebrovascular accidents,1,2 OSA and coronary artery disease (CAD) share many risk factors such as male gender, obesity and advancing age.3 The prevalence of hypertension and CAD has been shown to correlate strongly with the percent of sleep time spent hypoxemic and the apnea-hypopnea index (AHI).4 In the same study, there was also a modestly increased prevalence of stroke with OSA. Patients with OSA have increased overnight platelet aggregation,5 elevated whole blood viscosity 6 and elevated daytime and overnight fibrinogen levels,7 all of which may contribute towards adverse vascular events.

In addition to the difficulties encountered during endotracheal intubation, patients with OSA are sensitive to the central depressant medications, particularly narcotics.8 Intravenous morphine use postoperatively results in a higher incidence of postoperative sleep disordered breathing as compared to regional anesthesia.9 Episodic hypoxemia has been shown to occur both early and later (days 2 to 5) postoperatively.10,11 OSA may exacerbate this hypoxemia with deleterious effects on the cardiovascular system. While immediate postoperative complications can be intuitively attributed to negative effects of narcotics, sedatives or residual effects of anesthesia on upper airway muscles, later events are more likely related to rapid eye movement (REM) rebound.

Literature addressing the acute effects of sleep apnea in patients undergoing coronary artery bypass grafting (CABG) and other cardiac surgeries, which are commonly performed in patients with CAD, is sparse. The objective of this retrospective study is to compare the incidence of perioperative complications in patients with and without OSA who undergo cardiac surgery.

TABLE I.-Results of propensity score matching (continuous factors).

Materials and methods

Definitions

An apnea was defined as cessation of airflow lasting at least 10 s. A hypopnea was defined as a 10 s or longer period of 1) 50% reduction in airflow or 2) a 30% reduction in airflow which resulted in an arousal or a 4% desaturation. An AHI (5 defined OSA.

Inclusion criteria

The Cleveland Clinic Cardiac Surgery and Sleep Center databases were used to identify the patients who underwent an open heart surgery within two years of the date of the polysomnogram (PSG) between January 1995 and December 2000. The data collection for the study was approved by the Institutional review board at our institution. An assumption was made that if the surgery was performed within two years of the diagnosis of OSA, the patient had OSA at the time of the surgery. During this period 25 587 patients were identified in the cardiac surgery database of which 37 were diagnosed with OSA by PSG.

Data collection

Baseline variables recorded included demographics, type of cardiac surgery, body mass index (BMI), ejection fraction (EF), carotid artery disease, history of myocardial infarction (MI), smoking, presence of hypertension, and COPD. For patients that underwent PSG, variables like AHI, lowest oxygen saturation, hypoxic time during sleep (percentage of sleep time spent below 90% saturation) were also recorded. The clinical endpoints for this study were postoperative complications including: operating room (OR) and total tube time, frequency of reintubation, encephalopathy, postoperative infections and mediastinitis, ICU and hospital length of stay, perioperative mortality and morbidity.

Statistical analysis

The statistical analysis was divided into 2 phases. The first involved the creation of a sample from the 25 550 without OSA patients comparable, in terms of risk factors, to the sample of 37 patients with OSA. To balance the differences and reduce the bias when, comparing the 2 groups of patients, propensity analysis was used to select a sample from the patients without OSA with similar values of the covariates to that of patients with OSA.12 The matching was done on the basis of the sum of the absolute differences between cases and controls. The covariates used to compute the differences were: BMI, weight, gender, race, smoking, emergency, diabetes, COPD/asthma, preoperative hematocrit and cardiopulmonary bypass (CPB) time. These covariates were selected because they are either established cardiac risk factors or factors that could influence the outcomes.

Each of the 37 cases was matched to five controls within a distance of 0.001 units of the case.

The analyses are based on the sample of 222 (= 37 + 185). In order to check the effectiveness of the matching of the OSA and non- OSA patients the values of the covariates were compared using descriptive statistics and frequencies. Due to the lack of symmetry of the distributions, the medians and Wilcoxon rank sum test are reported. For categorical variables either the Chi-square or Fisher’s exact test were used. Table I shows the comparison for continuous covariates, while Table II compares the categorical covariates. Given the non-significance of the differences, it is clear that the matching was effective in balancing the two groups.

TABLE II.-Results of propensity score matching (categorical factors).

The second phase of the analysis was the comparison of outcomes between patients with and without OSA. The outcomes for the two groups were compared using either medians and the Wilcoxon test for continuous outcomes or the Fisher’s exact test (Tables III, IV). Additionally, among the patients with OSA, the associations between the severity of OSA by PSG vanables and the outcomes were analyzed using correlation or logistic regression. All analyses were done using SAS 9.0(SAS Institute Inc.,Cary, NC).

Results

From January 1995 to December 2000, among patients who underwent open-heart surgery, 37 patients were diagnosed by PSG to have OSA. These cases were matched with 185 controls who had not been diagnosed with OSA. The demographic and baseline comorbidities for both, the OSA and matched non-OSA groups, are outlined in tables I andII. For the OSA group, the median AHI was 16.1 (IQR: 7.2, 27.7), the median lowest saturation was 80.5 (IQR: 72.8, 85.5) and the median hypoxic time was 10 (IQR: 2.5, 24.8).

TABLE III.-OSA versus non-OSA patient outcomes after propensity score matching (categorical Outcomes).

TABLE IV.-OSA vs non OSA patient outcomes after propensity score matching (quantitative outcomes)

Among the categorical outcomes (TableIII), encephalopathy was more prevalent among patients with OSA (10.8% vs 1.08 %) p=0.008. Difference in infection rates were also significant, 10.8% in OSA group vs 2.7% in patients without OSA (p = 0.028). This difference however was mostly accounted for by the presence of mediastinitis (8.1% vs 1.08 %). Obesity is a well known independent risk factor for mediastinitis.13-16 Our study groups were matched for BMI and nonetheless showed higher rate of mediastinitis in the OSA group. This difference could not be attributed to hyperglycemia in the postoperative period. Although the monitoring and management of hyperglycemia in our study did not qualify as intensive the OSA group had lower mean glucose for the first three days postoperatively in comparison to the controls.

TABLE V.-. Glycemic control potoperative days 1-3.

Among the quantitative outcomes (TableIV), the ICU length of stay (Table V) was significantly (p=0.031) different with medians of 46.8 and 29.6 hours for the OSA and non-OSA groups, respectively. Hospital length of stay was only marginally different with medians of 11 \and 9 days. OR and total tube time, as well as the reintubation per patient were not signficant. There were 5 and 16 reintubations in the OSA and non-OSA groups, respectively, yielding average reintubations per patient of 0.135 and 0.086. No differences in the duration of ventilator support were noted to explain the higher rate of infections 18 in the OSA group and longer ICU stay.

Discussion

OSA is not generally acknowledged as a perioperative risk factor.19 Cross sectional and epidemiological studies indicate that asymptomatic OSA is common.20 As apparent from our study, the low number of PSGs performed as well as the low use of CPAP in patients with known OSA reflect the fact that OSA is an under-recognized condition. With known adverse cardiovascular effects of OSA and the lack of data about the impact of OSA in patients who undergo cardiac surgery, our study sought to fill in this important gap.

In a case-control study of patients with OSA who underwent hip or knee replacement surgeries, adverse post-op outcomes were higher in patients with OSA.21 However, there was no relationship between the severity of OSA and the occurrence of complications. In a case series of perioperative complications in patients with OSA, which included 7 patients who underwent CABG, most of the patients were managed with immediate CPAP therapy following extubation for 24 to 48 hours. Use of early CPAP has been shown to prevent major complications.22 In the first 2 patients, there was respiratory failure in 1 patient and severe hypoxemia with ventricular arrhythmias in the 2nd patient. A smaller series of 4 patients with OSA undergoing cardiac surgery also described the use of CPAP post- op for 5 days with no complications.23 In a prospective study evaluating the incidence of arrhythmia in patients with OSA who undergo CABG, the relative risk for atrial fibrillation with an oxygen desaturation index ≥5 was 2.8;24 however, the AHI did not correlate with atrial fibrillation.

Hypoxia has been long known to be implicated in postoperative infections. Our study did not in particular use desaturation indices in the postoperative period to explain the higher rate of infections. A strong independent association has also been known to exist between sleep apnea, visceral obesity, insulin resistance and hypercytokinemia, which may contribute to it’s pathological manifestations and sequale. Sleep apneic men had higher plasma concentrations of the adipose tissue-derived hormone, leptin, and of the inflammatory and insulin resistance-producing cytokines tumor necrosis factor-alpha and interleukin-6 than nonapneic obese men, who had intermediate values, or lean men, who had the lowest values.25 Additionally REM rebound has been suggested to contribute to wound breakdown and mental confusion besides hemodynamic instability, myocardial ischemia, infarction and stroke.26-30 Activation of inflammatory transcription factors by intermittent hypoxia/ reoxygenation (IHR) a hallmark of OSAS, was noted to have a significant correlation with neurocognitive function as well as improvement upon reversal of IHR in a rat model.31

Hypoxemia and sympathetic activation are two important consequences of OSA 32-34 which may have a deleterious impact on the myocardium. The main trigger of myocardial ischemia in patients with OSA appears to be an increase in the oxygen demand associated with surges of heart rate and blood pressure.35 Mueller maneuvers, which simulate the effects of OSA, have been shown to cause more pronounced reductions in the left ventricular ejection fraction in subjects who have CAD as compared to those without CAD.36 Once reperfusion is established however, after a CABG, the heart may be less susceptible to hypoxemia, sympathetic activation and hemodynamic changes. This may account for the relative lack of adverse cardiac effects of OSA observed in the postoperative period in our group. Additionally, close monitoring and early interventions, in the ICU setting postoperatively, would be expected to decrease the consequences of hypoxemia, heart rate and blood pressure fluctuations. In fact, the complication rate in post cardiac surgery setting in a large institution such as ours is quite low. Therefore, the results of our study may not be generally applicable in the community hospital setting.

Congestive heart failure (CHF) with poor left ventricular function may be associated with sleep-disordered breathing, particularly central sleep apnea.37 Patients with CHF suffer from fluid retention and dependent edema. This may lead to accumulation of edema in the soft tissues of the neck and pharynx making the upper airway more narrow and collapsing in the supine position.38 The low prevalence of CHF in our group of patients may also have led to an underestimation of adverse outcomes due to OSA. A recent study reported a marked reduction in apneas in patients with OSA who had permanent pacemakers with an increase in the atrial pacing rate.39 A reduction in vagal tone induced by the overdrive pacing was postulated to have reduced the respiratory events. Our patients were on vasopressors and inotropes in the immediate post-op period. We wonder if these medications worked in a similar manner to reduce sleep-disordered breathing.

Our study has several limitations. Lack of awareness about the incidence of OSA in the general population and the cardiovascular population in particular, difficulties in clinical suspicion and diagnosis and limited use of Polysomnography make OSA a vastly underdiagnosed disease, to study. For similar reasons the number of cases in the study was very small resulting in a low power to detect differences. Additionally, retrospective studies will vastly underestimate the extent of this condition. A study that could detect a two fold increase (4% vs 2%) in mortality with 80% power would require approximately 500 OSA patients and 2500 matched controls.

Prospective studies are needed to determine if prior awareness of OSA and earlier interventions for these patients is associated with improved outcomes.

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R. KAW1 , J. GOLISH 1, S GHAMANDE2, R. BURGESS1, N. FOLDVARY1, E. WALKER1

1 Cleveland Clinic Foundation, Cleveland, OH, USA

2 West Virginia University, Morgantown, WV

Paper presented at the European Sleep Research Society Annual Congress at Innsbruck, Austria on September 15, 2006.

Address reprint requests to. R. Kaw MD Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, USA. E-mail: Kawr@ccf.org

Copyright Edizioni Minerva Medica Dec 2006

(c) 2006 Journal of Cardiovascular Surgery. Provided by ProQuest Information and Learning. All rights Reserved.