Authors
- Gagolkina, Ella RN, BN, GradDipCardiac
- Aromataris, Edoardo PhD
- Umapathysivam, Kandiah PhD
Abstract
Review question/objective: This review aims to identify the type and incidence of cardiopulmonary adverse events during procedural sedation and analgesia (PSA) in patients with obstructive sleep apnea (OSA).
To achieve this objective, this review will address the following question:
What is the incidence of perioperative cardiopulmonary adverse events associated with PSA in patients with OSA? To address this question, this review will consider studies that compare outcomes in OSA patients with non-OSA patients, as well as studies that report the adverse events of drugs used to induce PSA in OSA patients.
Background: Sleep is a natural state of rousable unconsciousness, which is marked by distinct phases of brainwave activity, and variations in muscle tone. Although muscle relaxation may be profound during sleep, in healthy individuals pharyngeal muscle tone maintains the airway structure, keeps the airway open and allows undisturbed breathing. Conversely, in patients with obstructive sleep apnea (OSA), the reduced tone of the pharyngeal muscles during sleep causes the upper airway to narrow making the airway tissues less rigid. Decreased rigidity leads to upper airway collapse, typically at the site where the narrowing is at its greatest. This obstruction to airflow will remain present until sleep is interrupted, that is the individual awakes and muscle tone is restored.1, 2 Frequent arousal from sleep and disrupted sleep at night are responsible for the daytime lethargy and sleepiness in OSA patients.3 A typical feature of OSA is loud snoring due to the vibration of the soft tissues of the pharynx, soft palate and uvula while air is accelerating through these structures.4 Snoring is a manifestation of partial airway obstruction. Apnea occurs when partial airway obstruction transforms into complete airway obstruction.4 Loud snoring alone is not confirmation of OSA.
Recurrent pharyngeal collapse during sleep causes periods of reduction (hypopnea) or complete cessation (apnea) of airflow, causing a decrease in the level of oxyhemoglobin (measured by the percentage of hemoglobin saturated with oxygen) and potentially hypoxemia.5 Apnea can be defined as the cessation of oronasal airflow for ten seconds or longer.6 Hypopnea is a period of reduction of >30% of airflow for at least 10 seconds and a >4% decrease in oxygen saturation.6
The severity of OSA is expressed as an apnea-hypopnea index (AHI), indicating the number of apnea or hypopnea events per hour.6, 7 The sum of apneas and hypopneas per hour of sleep is calculated and expressed as the AHI, giving a measure of the severity of the OSA (mild, 5-15 events per hour; moderate, 15-30 events per hour; and severe, >30 events per hour).6
Polysomnography (PSG) is considered to be the gold standard in diagnosis of OSA and is a comprehensive sleep study test that involves an overnight stay in a sleep laboratory with multichannel monitoring. Monitoring and recording of physiological parameters undertaken during PSG includes brain functioning via electroencephalogram (EEG), eye movements via electro-oculogram (EOG), heart rate, oxygen saturation (oximetry), nasal airflow and intensity of snoring, chin and leg electro-myography and respiration with abdominal and thoracic respiratory effort.7 However, polysomnography is an expensive and time consuming test.6 To assist anesthesiologists with risk assessment for OSA in pre-operative settings, various other screening questionnaires and clinical prediction models have been developed. For example, the STOP-BANG questionnaire is a user-friendly, validated (in surgical patients) screening tool for severe OSA in the immediate preoperative period when OSA is highly suspected. It uses a linear scale and does not require further investigation.8 Patients answer "yes" or "no" to eight questions focused on the most commonly associated risk factors for OSA.
Patients with OSA are thought to be at increased risk for peri-operative respiratory or cardiac complications9-13 and given the multiple adverse health associations, OSA syndrome poses a potential concern for anesthesiologists, sedationists and proceduralists. Large, population-based, epidemiological cohort studies have established that there is a high prevalence of undiagnosed OSA in adults.14-17 Young et al. used Wisconsin Sleep Cohort Study data to estimate the prevalence of sleep disordered breathing in middle-aged, adult populations and found a prevalence of up to 5% of adults having undiagnosed OSA.7,18 This observation was consistent across both Western and Asian populations. By contrast, other studies have found that the prevalence of OSA is higher in men (4%) than women (2%).7,19 OSA is strongly associated with obesity6,20 and increasing age.18, 21, 22 Among obese patients (BMI>40 kg/m2), the prevalence of OSA is as high as 98%.23 The prevalence of OSA is much higher (>50%) in patients with cardiac or metabolic disorders than in the general population.7 The prevalence of OSA in surgical patients is higher than in the general population,17, 24 and undiagnosed OSA is associated with increased perioperative morbidity and mortality.9
Anesthesia, when established, is a state of unrousable unconsciousness. The effects of anesthesia on airway muscular tone are similar to those described for OSA, so much so that the homogenous and profound loss of pharyngeal muscle tone may, if left untreated, result in asphyxia.3, 25, 26 Thus, maintenance of airway patency during sleep is a shared concern among anesthesiologists and sleep physicians, as both anesthesia and sleep predispose the upper airway to obstruction, mainly due to a loss of a wakeful pharyngeal tone.3 Eastwood et al27 have demonstrated an association between increased upper airway collapsibility and increased depth of sedation or anesthesia when using the anesthetic/hypnotic sedative drug propofol.
Procedural sedation and analgesia (PSA), with or without the addition of local anesthesia, may be administered to help patients tolerate painful, uncomfortable or otherwise distressing medical procedures. Unlike general anesthesia, patients undergoing PSA are required to maintain adequate control of airway and respiratory function without the assistance of airway devices or mechanical ventilation. Sedative and anesthetic medications produce a dose dependent depression of the arousal responses that usually protect against asphyxia.28 As a result, patients with OSA receiving PSA are under increased risk of peri-operative complications. Gupta et al9 concluded that adverse postoperative outcomes occurred at a higher rate in patients with diagnosed OSA undergoing anesthesia for hip or knee replacement. However, there is limited evidence available supporting the increased risk of peri-operative side effects among the OSA population receiving PSA. This systematic review will focus on peri-operative cardiopulmonary complications in patients diagnosed with OSA following sedation and analgesia administration.
Procedural sedation is induced by the administration of drug(s), that induce analgesia, anxiolysis, amnesia, sleepiness and relaxation. Drugs used intravenously to induce PSA include opioids (e.g. fentanyl), benzodiazepines (e.g. midazolam, diazepam), propofol, ketamine and dexmedetomidine.29,30 Such drugs may be used as a sole agent or in various combinations. Examples of procedures that may be undertaken with intravenous PSA include diagnostic and therapeutic procedures such as colonoscopy, bone marrow biopsy, cardiac studies, endoscopy, bronchoscopy and dental procedures.31-35
Known risks of procedural sedation include respiratory events, such as hypoventilation and progressive upper airways obstruction leading to apnea or hypopnea.36 This may lead to hypoxemia and hypercarbia.36, 37 In non-anesthetized patients, hypoxemia and hypercarbia stimulate ventilation and increased respiratory effort breaks the cycle of airway obstruction.36 Drug-induced sedation and analgesia can block the normal arousal and awakening in response to airway obstruction.3 In sedated patients normal arousal mechanisms can be suppressed when airway obstruction develops, leading to severe hypoxemia and hypercarbia, and potentially predisposing patients to hypo/hypertension, bradycardia/tachycardia and myocardial ischemia and ultimately to respiratory and cardiac arrest.3, 38, 39
A preliminary literature search of EMBASE, MEDLINE and the JBI and Cochrane libraries has been undertaken. One systematic review and one meta-analysis relating to the association between sedation/anesthesia and obstructive sleep apnea were identified.40,41 Both reviews were specific to patients with OSA receiving anesthetic agents for surgical procedures (orthopaedic, general surgical abdominal, gynaecological, bariatric, neurosurgical, vascular, thoracic, ENT and other types of elective surgery).
The aim of this systematic review is to determine the relationship between cardiopulmonary adverse events in patients with and without OSA, who are undergoing diagnostic and/or therapeutic procedures (including, but not limited to, colonoscopy, bone marrow biopsy, cardiac studies, endoscopy, bronchoscopy or dental procedures) and receiving midazolam and fentanyl PSA. Studies on patients undertaking surgical procedures under general anesthesia will be excluded from this review. Diagnosis of OSA will be determined by formal sleep study, or against the STOP-BANG criteria for those patients deemed at high risk of sleep apnea.42 This systematic review is needed so the burden of morbidity and mortality among OSA populations in settings where PSA is administered by both anesthesiologists and non-anesthesiologists can be determined.
Article Content
Inclusion criteria
Types of participants
This review will consider studies of participants who are:
1. 18 years and older;
2. formally diagnosed with, or at risk for OSA (as determined by formal sleep study, or assessment against the STOP-BANG criteria); and
3. undergoing a diagnostic or therapeutic procedure with intravenous PSA.
Procedures that may be performed under PSA include, but are not limited to, bone marrow biopsy, colonoscopy, cardiac studies, endoscopy, bronchoscopy, minor plastic surgery, vascular stenting, and urological procedures.
Studies on OSA patients receiving sedation for drug induced sleep studies to examine upper airways or receiving general anesthesia will be excluded from this review.
Types of intervention(s)
The incidence of perioperative cardiopulmonary adverse events associated with PSA including:
1. in control (non-OSA) and OSA populations
2. studies involving (1) midazolam or fentanyl alone, or in combination with or without local anesthesia as compared to (2) PSA using propofol, with or without supplementary drugs including midazolam and fentanyl, with or without local anesthesia.
Studies in which propofol is the primary agent used for sedation, as assessed by the authors, will be allocated to the propofol group.
Types of outcomes
This review will consider studies that include the outcome measures (adverse events) as listed below. Criteria used to define these events may vary between published studies. Criteria used in each study will be reviewed and considered in an assessment of heterogeneity between studies.
Cardiovascular events:
* hyper/hypotension (20% or greater increase (hypertension) or decrease (hypotension) in the pre-procedural blood pressure value or any single systolic blood pressure reading below 80 mmHg or above 160 mmHg)
* significant arrhythmias (e.g. AV heart block, ventricular tachycardia, atrial fibrillation)
* brady/tachycardia (e.g. < 50 beats per minute, or >=120 beats per minute)
* chest pain
* cardiac arrest
* heart failure
Pulmonary events:
* loss of airway patency
* hypoventilation (e.g. respiratory rate <= 8 breaths per minute)
* oxygen desaturation (e.g. saturation of oxygen, sPO2, <=92%).
* laryngospasm
* bronchospasm
* aspiration
Mortality and morbidity
Types of studies
This review will consider both experimental and epidemiological study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies for inclusion.
Search strategy
The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Studies published in English will be considered for inclusion in this review. Obstructive sleep apnea was first described in the literature more than 100 years ago. The disorder was rediscovered and recognised as a medical condition and described in the medical literature only in 1965. Studies published from 1965 until the present time (2013) will be included in the search.
The databases to be searched include:
PubMed, EMBASE, CINAHL, Cochrane Central Trials Register and Scopus.
The search for unpublished studies will include:
Current Controlled Trials, ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry (anzctr.org.au), and ProQuest Dissertations and Theses.
Initial keywords to be used will be:
Obstructive sleep apnea, sleep apnea syndrome, sleep apnea, sleep disordered breathing, sleep hypopnea, OSA, OSAH, apnea hypopnea syndrome, hypersomnia with periodic respirations, upper airway, upper airway resistance, upper airway obstruction;
Short acting anesthesia, sedation, conscious sedation, propofol, diprivan, fentanyl, midazolam neuroleptanalgesia, anesthesia and analgesia, anesthetic
Safety, complication(s), morbidity, mortality, adverse events, postoperative complications.
Assessment of methodological quality
Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardised critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.
Data collection
Data will be extracted from papers included in the review using the standardised data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives.
Data synthesis
Quantitative data will, where possible, be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also examined via subgroup analyses isolating the different means of diagnosing OSA patients and the severity of OSA, where possible. Where statistical pooling is not possible the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate.
Conflicts of interest
None
Acknowledgments
My external supervisor Dr Ian Banks, MB BS, MD, FRCA, FANZCA, Consultant Anaesthetist, Royal Adelaide Hospital, for mentorship and guidance in the preparation of this paper.
For assistance as a secondary reviewer Ms Jennifer Costi, Medical Educator, Modbury Hospital.
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Appendix I: Appraisal instruments
Appendix II: Data extraction instruments
MAStARI data extraction instrument[Context Link]
Keywords: Obstructive sleep apnoea; sleep disordered breathing; sedation; analgesia; fentanyl; midazolam; propofol; safety; adverse events