Opioids are widely prescribed for treatment of moderate to severe pain after surgery. While opioids are generally safe for most patients, they may lead to acute respiratory depression in unmonitored settings such as a surgical ward. The incidence of postoperative opioid overdose has doubled from 0.6 to 1.1 per 1000 operative cases from 2002 to 2011 and patients with postoperative opioid overdose have a 4-fold higher mortality rate.1 Of the opioid-related adverse drug events in the Joint Commission’s Sentinel Event database between 2004 and 2011, 47% were wrong-dose medication errors, 29% were related to improper monitoring of the patient, and 11% were related to excessive dosing, medication interactions, and adverse drug reactions.2 In a review of 92 closed claims related to opioid-induced respiratory depression, 97% of claims could have been prevented with (1) improvements in assessment of sedation level; (2) monitoring of oxygenation and ventilation; and (3) early response and intervention, particularly within the first 24 hours postoperatively.3
For these reasons, the Anesthesia Patient Safety Foundation,4 the Joint Commission,2 and the American Society for Pain Management Nursing5 have called for continuous electronic monitoring for all patients receiving opioids in the postoperative period. Due to the rarity of respiratory depression, the recommendations are based mainly on consensus opinion because there are limited studies on the efficacy of postoperative monitoring. There is a need to review and summarize the existing available data and evidence on pulse oximetry and capnography.
Pulse oximetry is a noninvasive method for measuring heart rate and oxygen saturation in the blood. The value in pulse oximetry monitoring lies in its ability to provide an estimation of the degree of hypoxemia in arterial blood. Capnography is a noninvasive method for estimating the partial pressure of carbon dioxide in the arterial blood. Capnography is composed of end-tidal capnography that measures partial pressure of carbon dioxide in exhaled gases and transcutaneous capnography that measures partial pressure of carbon dioxide via a heated electrochemical sensor applied to the skin. The benefits of capnography lie in the ability to monitor ventilatory status through changes in end-tidal or transcutaneous CO2 from baseline, respiratory rate, and the occurrence of breathing pauses (hypopnea and apnea) that may occur as a result of opioid use. In the operating room, the use of pulse oximetry and capnography have significantly improved patient safety and have been accepted as the standard of practice.6,7 At present, these monitors have not been accepted as the standard of postoperative care in the surgical ward.
In this systematic review, we summarize the current state of knowledge on the effectiveness of continuous pulse oximetry (CPOX) versus routine nursing care and the effectiveness of continuous capnography with and without pulse oximetry for the detection of postoperative respiratory depression (PORD) and prevention of postoperative adverse events.
Search Strategy and Study Selection
We screened published articles evaluating the effectiveness of CPOX and/or capnography monitoring for detection of PORD and prevention of postoperative adverse events. The literature search and review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, and the search strategy was implemented with the help of an expert librarian familiar with the literature search. We searched the literature databases PubMed-MEDLINE (1946 to May 2017), MEDLINE in-process, and other nonindexed citations (to May 2017), Embase and Embase Classic (1947 to May 2017), Cochrane Central Register of Controlled Trials (to May 2017), Cochrane database of systematic reviews (to May 2017), and PubMed (to May 2017).
The search used the Medical Subject Heading keywords “monitoring,” “oximetry,” “capnography,” “clinical alarms,” “opioid analgesics,” “patient-controlled analgesia,” “respiratory insufficiency,” “pulmonary ventilation,” “anoxia,” “apnea,” “dyspnea,” “hypoventilation,” “work of breathing,” “respiratory rate,” “vital signs,” “oxygen saturation,” “adverse events,” “rescue,” “intensive care unit,” “perioperative care,” “postoperative care,” “sudden cardiac death,” “cardiopulmonary arrest,” “heart arrest,” “respiratory arrest,” and “death.”
The criteria to include studies in our review were as follows: (1) adult surgical patients (>18 years old); (2) prescribed opioids during the postoperative period; (3) monitored with CPOX and/or capnography; (4) available reports on oxygen desaturation, bradypnea, hypercarbia, rescue team activation, adverse events, intensive care unit (ICU) transfers, or mortality; and (5) published studies in the English language. The exclusion criteria were as follows: (1) case reports and (2) studies not meeting the inclusion criteria.
Studies were selected independently by 2 reviewers (T.L., M.N.), who screened the titles and abstracts to determine whether the studies met the eligibility criteria. Full text copies of articles deemed to be potentially relevant were retrieved. Duplicate publications were excluded. A citation search by manual review of references from primary or review articles was performed.
Data extraction was performed independently by 2 reviewers (T.L., M.N.). Any disagreements were resolved by consensus or by consulting another author (F.C.). The following information was collected from each study: author, year of publication, type of study design, sample size of the monitored group, and type of monitoring.
Study Quality Assessment
All included studies were graded for strength of evidence according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence 2011.8 The classification was as follows: level I: systematic review of randomized trials; level II: randomized trial or observational study with dramatic effect; level III: nonrandomized controlled cohort; level IV: case-series, case–control studies, or historically controlled studies; and level V: mechanism-based reasoning.
The measure of detection for PORD was the weighted odds ratio (OR) with 95% confidence interval (CI) and the weighted risk ratio (RR) with 95% CI for the ICU transfer. The Mantel-Haenszel (M-H) method was used to combine dichotomous events. By extracting the crude data, the OR and RR for the individual studies was recalculated and then pooled across studies using random-effects modeling. The results were displayed as forest plots using Review manager (RevMan, version 5.3., Copenhagen, Denmark). P < .05 was considered statistically significant. Heterogeneity across studies was investigated for each adverse event by calculating I2.
Our primary outcome measure was PORD and adverse events. Respiratory depression was defined as an episode of oxygen desaturation, bradypnea, or hypercarbia. Adverse events were defined as any rescue team activation, ICU transfer, or death. Postoperative period was defined as the time from admission to a surgical unit after discharge from the postanesthesia care unit. Continuous monitoring was defined as the uninterrupted application of pulse oximetry and/or capnography with collection of serial oxygen saturation and end-tidal/transcutaneous CO2 and respiratory rate measurements, respectively. Routine nursing care was defined as nurses obtaining vital signs, typically at 4- to 6-hour intervals.
The review was conducted according to the PRISMA guidelines. Our search strategy is listed in Figure 1. Our initial electronic search identified 11,583 citations. After screening titles and abstracts, 11,527 studies were excluded for not meeting the predetermined eligibility criteria. Of the remaining 56 studies, 47 were excluded and the reasons are listed in Figure 1. Articles were most often excluded because they did not study the monitoring intervention of interest. In total, 9 studies (2 randomized controlled trials [RCTs], 1 prospective historical controlled trial, 5 prospective observational studies, and 1 retrospective observational study) were included in this systematic review. According to the Oxford Centre for Evidence-Based Medicine Levels of Evidence 2011,8 the strength of the evidence in the 9 studies was low to moderate.
Out of the 9 included studies, 4 examined the effectiveness of CPOX monitoring versus routine nursing care9–12 and 5 examined the effectiveness of continuous capnography with or without pulse oximetry13–17 for the detection of PORD or prevention of adverse events. The characteristics and main findings of the 9 studies are shown in Tables 1 and 2 (sorted according to mode of monitoring, methodological quality, and sample size). Of the 4 studies examining the impact of CPOX, 1 was a prospective RCT,9 1 was a prospective, historical controlled trial,10 and 2 were observational studies.11,12 Of the 5 studies examining the impact of continuous capnography and CPOX, 1 was a prospective RCT,14 3 were prospective observational studies,13,16,17 and 1 was a retrospective observational study.15
Use of Pulse Oximetry Monitoring
Of the 4 studies examining the performance of CPOX monitoring versus routine nursing checks, 2 evaluated the impact on rescue team activation, ICU admission, or mortality,9,10 and 2 evaluated the impact for detection of oxygen desaturation versus intermittent nursing checks.11,12
The strongest evidence examining the use of CPOX is derived from a nonblinded RCT study of 1218 patients from a 33-bed postcardiothoracic surgery care floor.9 Ochroch et al9 found that CPOX monitoring did not reduce transfer to ICU (CPOX versus control: 6.7% vs 8.4%; RR: 0.81; 95% CI, 0.54–1.2; P = .29) or mortality (CPOX versus control: 2.3% vs 2.2%) versus standard nursing care (Table 3). However, the use of CPOX monitoring significantly reduced the number of patients transferred to the ICU for pulmonary reasons (CPOX versus control: 1.3% vs 4.2%; RR: 0.32; 95% CI, 0.15–0.69; P = .004). Of those transferred to ICU, the CPOX group had significantly shorter ICU stays and overall costs.9
In a prospective, historical controlled trial, Taenzer et al10 implemented a patient surveillance system using CPOX monitoring with nursing notifications via pager when physiologic limits were violated. This patient surveillance system was implemented in a 36-bed orthopedic unit for 10 months and data were compared to the 11 months before implementation of the system and concurrent data on 2 other postoperative units.10 The use of CPOX monitoring was associated with a significant reduction in rescue events from 3.4 to 1.2 per 1000 patient discharges and ICU transfers from 5.6 to 2.9 per 1000 patient days, whereas the comparison units had no change.10 This correlated with a reduced need for rescue team activation by 65% and ICU transfers by 48% (Table 3).
Overall, comparing the CPOX group versus the standard monitoring group, there was a trend toward reduced ICU transfers in the CPOX group (RR 0.66, CI, 0.42–1.01; P = .06; Table 3).
Two observational studies compared the use of CPOX to routine nursing care (spot-check vitals every 4–6 hours) for detection of oxygen desaturation.11,12 In 833 patients after noncardiac surgery, Sun et al11 determined that oxygen desaturation was common (21% had >10 min/h with oxygen saturation [Spo2] <90%) and prolonged (37% had at least 1 episode of Spo2 <90% for an hour or more). Nurses missed 90% of hypoxemic episodes in which saturation was <90% for at least 1 hour.11 The odds of recognizing desaturation (Spo2 <90%) was 15 times higher in the CPOX group when compared to the standard monitoring group (OR, 15.7; 95% CI, 10.6–23.2; P < .00001; Table 3). In 16 patients considered to be at high risk for deterioration, Taenzer et al12 showed that manual charted oxygen saturations every 4 hours were on average 6.5% higher than those recorded with CPOX.
Use of Capnography Monitoring
Of the 5 studies evaluating the use of continuous capnography, 1 RCT examined the effectiveness of continuous capnography without pulse oximetry versus routine nursing care and 4 studies evaluated the effectiveness of continuous capnography with CPOX for detecting PORD. Pooled data from 3 capnography studies13,14,16 showed that continuous capnography versus CPOX monitoring identified 8.6% more PORD events (bradypnea versus desaturation <90% >1 hour) (CO2 group versus Spo2 group: 11.5% vs 2.8%; P < .00001). The odds of recognizing PORD was 5.8 times higher in the capnography versus the CPOX group (OR: 5.83, 95% CI, 3.54–9.63; P < .00001, I2 0%) (Figure 2).
In a RCT of opioid-naive postoperative orthopedic patients, 54 patients were randomized in the postanesthesia care unit to either postoperative monitoring with continuous capnography group (n = 29) or control group (spot-check pulse oximetry and respiration rate assessment by observation or auscultation every 4 hours) (n = 25).14 PORD was defined as a respiratory rate <6 per minute, apnea >20 seconds, end-tidal CO2 greater than 60 mm Hg, or Spo2 <88%. The capnography group and the control group had no significant differences in opioid use on the day of surgery or on the first postoperative day. PORD was detected at a higher rate in the capnography group versus the control group (140 vs 6 respiratory depression events; P = .03).14 The majority of PORD events in Hutchison’s study was detected by capnography when patients breathed at 6 or less per minute or had repeated apneas longer than 20 seconds.14 The other 2 indicators of PORD (an end-tidal CO2 level >60 mm Hg and oxygen saturation <88%) did not contribute to the outcomes measured, suggesting that they may be less-sensitive indicators of changes in respiratory function when supplemental oxygen is in use.14
Four observational studies support the combined use of continuous capnography and CPOX for the detection of PORD.13,15–17 McCarter et al16 showed that in patients receiving intravenous (IV) patient-controlled analgesia (PCA) opioids, continuous capnography identified a 1.4% (9 of 634) incidence of PORD (defined as respiratory rate <6 per minute, apnea >20 seconds or end-tidal CO2 >50 mm Hg). Of the 9 patients with PORD, all were receiving supplemental oxygen therapy, and all of the PORD events were detected by continuous capnography, and none was detected by CPOX. In 44% (4 of 9) cases of PORD, naloxone was given and the rescue team was activated.16
Overdyk et al13 found that in 178 postsurgical patients receiving IV PCA opioids, continuous capnography identified a 41% incidence of bradypnea (defined as RR <10 × 3 minutes) and CPOX detected a 12% incidence of desaturation (defined as Spo2 < 90%). Of the 15 patients in this study receiving supplemental oxygen, 11 patients had significantly prolonged (3 or more minutes) episodes of bradypnea, while only 4 patients had coincident desaturation events (P = .01).
Similarly, Kopka et al17 demonstrated that in patients receiving IV PCA morphine and supplemental oxygen, transcutaneous CO2 monitoring identified significantly prolonged (average 6.6 hours) hypercarbia (defined as CO2 >45 mm Hg) despite normal oxygen saturation readings.
Finally, Maddox et al15 showed that in a 33-month period, an IV safety system that combined PCA pump and a continuous capnography/pulse oximetry module with preset alarms (HR <50 beats per min or >120 beats per min; Spo2 <90%, RR <10 breaths per min, Etco2 >60 mm Hg, or apnea >30 seconds) was able to identify 16 patients who required intervention by a respiratory therapist.
This systematic review and meta-analysis summarizes the evidence concerning the use of CPOX versus routine nursing care and continuous capnography combined with or without CPOX monitoring for the detection of PORD and/or adverse events. Comparing the CPOX group versus the standard monitoring group, the odds of recognizing desaturation (Spo2<90% >1 hour) with CPOX was 15 times higher (P < .00001) and there was a trend toward less ICU transfer (RR, 0.66; P = .06). The effect of CPOX on rescue team activation and mortality is inconclusive. Pooled data from 3 capnography studies showed that the continuous capnography group identified 8.8% more PORD events versus the pulse oximetry group (CO2 group versus Spo2 group: 11.5% vs 2.8%; P < .00001). The odds of recognizing PORD was almost 6 times higher in the capnography versus the pulse oximetry group (OR: 5.83, 95% CI, 3.54–9.63; P < .00001). No studies examined the impact of continuous capnography on reducing rescue team activation, ICU transfers, or mortality.
The advantages of CPOX lie in its ability to accurately detect hypoxemia versus routine nursing care, low cost, ease of use, and ease of interpretation. Two observational studies illustrated that periodic spot-checks of vitals every 4–6 hours grossly underestimates postoperative hypoxemia.11,12 Given that acute hypoxemia (and not hypercarbia) is the most serious threat to human life, and that the most important factor for the success of rescue teams is the timely detection of patient deterioration,18 it is important that Spo2 measurements reflect true patient physiology. Early warning scores depend on an accurate assessment of Spo2 to determine whether a rescue team should be activated.19 By providing an accurate Spo2 measurement, CPOX may allow for advance recognition of patient deterioration and prompt activation of rescue teams in surgical ward; however, this hypothesis needs further testing. More evidence from RCTs is important and needed, but may not be necessary for acceptance as a safety practice.20 Pulse oximetry was adopted in the operating room without good evidence that it reduced adverse outcomes but is currently standard of practice because it has compelling benefit without harm.
CPOX has its limitations. First, the evidence is inconclusive on whether CPOX has an impact on clinically relevant outcomes. Ochroch et al9 found that CPOX monitoring per se did not reduce ICU transfer or mortality. Similarly, a Cochrane systematic review examining the use of pulse oximetry during and after surgery found that CPOX is superior at detecting hypoxemia but did not reduce the risk of complications or dying after anesthesia.21 In a closed claims analysis, Lee et al3 found that in one-third of the claims on PORD, CPOX monitoring was in use at the time of the PORD event.
It may be possible that pulse oximetry monitoring without nursing notification is insufficient to detect postoperative cardiopulmonary complications. Electronic patient surveillance systems may provide a qualitatively superior method of continuous monitoring by delivering alert pages to nurses to notify desaturation. Taenzer et al12,22 demonstrated that CPOX monitoring with a centralized alarm warning system reduced rescue events and ICU transfers. Monitoring oxygen saturation with alerts may need to be transmitted in real time to a centralized nurse’s station or to the nurse’s handheld device/pager to proactively alert staff of patient deterioration. The differences in the study results with respect to ICU transfers may also be dependent on the effort of the rescue team to remedy a clinical problem on the floor versus transfer all patients to the ICU immediately. ICU transfer results may be dependent on hospital policy.
Second, oxygen desaturation lags behind hypoventilation and is a late sign of postoperative opioid-induced respiratory depression when supplemental oxygen is administered.23–25 When arterial Pco2 rises secondary to hypoventilation, so does alveolar Pco2, resulting in a fall in alveolar Po2, as per the alveolar gas equation. When patients are breathing room air, oxygen desaturations will occur early and pulse oximetry is a sensitive indicator for hypoventilation. On the contrary, when supplemental oxygen is used, the alveolar Po2 is higher and alveolar Pco2 needs to rise further before hypoxemia and desaturation occurs.26 A mathematical model demonstrates that with a fraction of inspired oxygen (Fio2) of 0.21, by the time alveolar Pco2 has increased to 65 mm Hg, alveolar Po2 will decrease to 60 mm Hg. In contrast, with a Fio2of 0.3, alveolar Po2 is maintained at 100 mm Hg when Paco2 is 90 mm Hg.23 Oxygen saturation level in the presence of supplemental oxygen imparts late information on the adequacy of ventilation. It provides a false sense of security27 and may delay appropriate respiratory care.28
Continuous Capnography Monitoring
It is important to recognize that oxygenation and ventilation are 2 distinct physiologic processes. Spo2 reflects oxygenation while Etco2 and RR reflect ventilation; 1 parameter may be normal while the other is abnormal.15 Measuring oxygenation or ventilation alone may not provide a complete picture of respiratory status.
In our systematic review, we found that when continuous capnography monitoring was used in conjunction with CPOX, capnography provided additional information on ventilation that helped herald respiratory depression before oxygen desaturation when supplemental oxygen was administered.13–16 These findings mirror a RCT examining the use of capnography in emergency department procedural sedation.29 Capnography was able to identify respiratory depression before clinical examination and before oxygen desaturation and decreases the rate of sedation-associated hypoxia.7,29 In the pediatric postanesthesia care unit, patients with capnography monitoring had significantly fewer hypopnea and apnea episodes versus routine monitoring with CPOX.30 Together, these studies suggest that continuous capnography should be used in conjunction with pulse oximetry particularly in the presence of supplemental oxygen.25,31 Integrating oxygenation (Spo2, HR) and ventilation (RR, Etco2) parameters in the form of an index may help identify clinically significant respiratory changes earlier and more reliably.32
In addition to alerting clinicians of patients with impending respiratory failure, respiratory rate had the added benefit of helping nurses individualize pain management regimens.15 Patients with low respiratory rate received less opioids and patients in severe pain with adequate respiratory rate received more. Continuous capnography allowed for better titration of narcotics and improved pain management.15
Capnography has its limitations. No studies have been published on the effectiveness of capnography on clinically important outcomes (rescue team activation, ICU transfers, or mortality). Etco2 may not accurately reflect the Paco2 in nonintubated patients in the setting of low-tidal volume breathing or mouth breathing. End-tidal CO2 reading has been shown to correlate with Paco2 only on a full vital capacity breath.33 Thus, the Etco2 value may lie in trend analysis. Transcutaneous capnography, on the other hand, has the advantages of providing an accurate reflection Paco2.34–36 Capnography may require extra training of staff members before implementation.14 The nasal cannula may impede activities of daily living and may hinder postoperative ambulation.14 In patients with OSA, it is unclear whether accurate readings of end-tidal CO2 can be obtained when a continuous positive airway pressure device is used at the same time.14 Transcutaneous CO2 monitors may need to be resited regularly, erythema can occur, and monitors may require repeated calibration and time to calibrate.37 Implementing continuous monitoring comes with obstacles, and similar to any new technology, monitoring with continuous capnography ± pulse oximetry requires careful risk–benefit analysis (Table 4).
Strengths and Limitations of the Systematic Review
This is the first systematic review to summarize the evidence of the effectiveness of CPOX versus routine nursing care and the effectiveness of continuous capnography with CPOX for detecting PORD and preventing adverse events. The limitations of this review included the variable methodological quality of the studies with low to modest level of evidence. In the CPOX studies, it is not possible to directly attribute oxygen desaturation to respiratory depression. Other than hypoventilation, oxygen desaturation can be caused by decreased Fio2, ventilation-perfusion mismatch, shunt, diffusion defects, and increased O2 consumption. Due to the paucity of evidence, it is difficult to make any strong recommendations regarding best practice with respect to type of monitoring for PORD.
Recognizing the patient at risk for PORD would allow for better triaging of monitoring resources. Multiple patient,1,40–53 surgical,1,3,44,47,48,54,55 and anesthetic3,45,47,55–58 risk factors for respiratory depression have been identified (Supplemental Digital Content, Table 1, https://links.lww.com/AA/C69). Improved education on respiratory depression and monitoring is needed. Predicting patients at risk is challenging and may be inaccurate. At the same time, significant costs are involved with a nation-wide shift to mandatory continuous monitoring for all postoperative patients and even greater costs in installing surveillance systems based on continuous monitoring data. There is a need for further research on whether all patients or only high-risk patients should be monitored, the cost–benefit ratio of monitoring every patient versus high-risk patients, how can we better define high risk, and comparative effectiveness research of monitoring technology on clinically relevant outcomes (rescue team activation, ICU transfer, mortality).
The Joint Commission issued a 2013 sentinel event alert implicating alarm fatigue in 98 adverse events, including 80 deaths.59 To indicate a serious adverse event, alarm criterion based on a single variable is simpler, but may be a less-sensitive alternative.60 Alarm thresholds may have to be customized for specific clinical units, group of patients, or individual patients.61–63 Further research examining which physiologic (or a combination) parameters to monitor and their appropriate alarm limits are needed to find the best balance between sensitivity and specificity, while controlling false alarms.61,64
Patient monitors with smart technology (ie, acoustic respiratory rate monitors,65 noninvasive respiratory volume monitors,66,67 single plate sensing units placed under the mattress to detect a patient’s heart rate, respiratory rate and motion,68,69 alarm management technology that incorporate several physiologic parameters and reduces clinically insignificant respiratory alarms)38,39,69,70 are available or on the horizon. A balance may be needed to find the best technology that is able to detect PORD and other common causes of deterioration postoperatively that require escalation of care.
Comparing the CPOX group versus the standard monitoring group, the odds of recognizing desaturation (Spo2 <90% >1h) was 15 times higher and there was a trend towards less ICU transfers. The evidence on whether CPOX leads to less rescue team activation and mortality is inconclusive. The odds of recognizing PORD was almost 6 times higher in the capnography versus the pulse oximetry group. No studies examined the impact of continuous capnography on reducing rescue team activation, ICU transfers, or mortality. There is preliminary evidence to support the use of CPOX and capnography in postoperative monitoring to prevent respiratory depression and adverse events. Further research with well-designed, adequately powered RCTs is needed to address the effectiveness of CPOX and capnography monitoring on patient outcomes.
The authors thank Marina Englesakis, BA (Hons), MLIS, Information Specialist, Surgical Divisions, Neuroscience & Medical Education, Health Sciences Library, University Health Network, Toronto, ON, Canada, for her assistance with the literature search.
Name: Thach Lam, MD.
Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.
Conflicts of Interest: None.
Name: Mahesh Nagappa, MD.
Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.
Conflicts of Interest: None.
Name: Jean Wong, MD.
Contribution: This author helped write the manuscript.
Conflicts of Interest: J. Wong received research grants from Ontario Ministry of Health and Long-Term Care Innovation Fund, Anesthesia Patient Safety Foundation, and Acacia Pharma.
Name: Mandeep Singh, MD, MSc.
Contribution: This author helped write the manuscript.
Conflicts of Interest: None.
Name: David Wong, MD.
Contribution: This author helped write the manuscript.
Conflicts of Interest: None.
Name: Frances Chung, MBBS.
Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.
Conflicts of Interest: F. Chung received research grants from Ontario Ministry of Health and Long-Term Care Innovation Fund, University Health Network Foundation, ResMed Foundation, Acacia Pharma, Medtronic; STOP Bang tool: proprietary to University Health Network; Royalties from Up-To-Date.
This manuscript was handled by: David Hillman, MD.
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