Confounding Variables and Generalizability in EMS Research

Reference: Snyder BD, Van Dyke MR, Walker RG, et al. Association of small adult ventilation bags with return of spontaneous circulation in out of hospital cardiac arrest. Resuscitation 2023. Date: January 11, 2024 Guest Skeptic: Dr. Chris Root is an EMS fellow in the Department of Emergency Medicine at the University of New Mexico Health Sciences Center in Albuquerque, NM. He is also a flight physician with UNM’s aeromedical service, Lifeguard Air Emergency Services. Prior to earning his MD, he worked as a paramedic in the New York City 911 system. Case: You are dispatched to an out-of-hospital cardiac arrest (OHCA). The patient is a 54-year-old man who collapsed in front of his family after complaining of chest pain for several hours. On your arrival, first responders from the fire department are performing high-quality basic cardiac life support. You continue with compressions and defibrillations and your partner places an advanced airway. Your EMS agency has equipped you with small-volume adult bag-valve masks (BVMs), the first responders have been utilizing a standard adult BVM thus far during the resuscitation. Your partner asks you which of the two BVMs you should use to continue the resuscitation. Background: There is continuing debate regarding the appropriate ventilation strategy for OHCAs. Common commercially available BVMs can deliver volumes that exceed normal tidal volumes. Some have argued in favor of using smaller BVMs to avoid hyperventilation. The issue of BVM ventilation in the context of pre-oxygenation for endotracheal intubation was discussed on SGEM#281. Airway management in OHCA has also been covered in SGEM#247 and SGEM#396. We have looked at OHCA more than a dozen times on the SGEM. For a full list of check out the links below to the SGEM blogs:  SGEM#50:Under Pressure Journal Club: Vasopressin, Steroids and Epinephrine in Cardiac Arrest SGEM#54:Baby It’s Cold Outside: Pre-hospital Therapeutic Hypothermia in Out of Hospital Cardiac Arrest SGEM#59:Can I Get a Witness: Family Members Present During CPR SGEM#64:Classic EM Paper: OPALS Study SGEM#107:Can’t Touch This: Hands on Defibrillation SGEM#136:CPR – Man or Machine? SGEM#143:Call Me Maybe for Bystander CPR SGEM#152:Movin’ on Up – Higher Floors, Lower Survival for OHCA SGEM#162:Not Stayin’ Alive More Often with Amiodarone or Lidocaine in OHCA SGEM#189:Bring Me to Life in OHCA SGEM#238:The Epi Don’t Work for OHCA SGEM#247:Supraglottic Airways Gonna Save You for an OHCA? SGEM#275:10th Avenue Freeze Out – Therapeutic Hypothermia after Non-Shockable Cardiac Arrest SGEM#306:Fire Brigade and the Staying Alive APP for OHCAs in Paris SGEM#314:OHCA – Should you Take ‘em on the Run Baby if you Don’t get ROSC? SGEM#329:Will Corticosteroids Help if…I Will Survive a Cardiac Arrest? SGEM#336:You Can’t Always Get What You Want – TTM2 Trial SGEM#344:We Will…We Will Cath You – But should We After an OHCA Without ST Elevations? SGEM#353:At the COCA, COCA for OHCA SGEM#380:OHCAs Happen and you’re head over heels – Head elevated during CPR? SGEM#396: And iGel myself I’m over you, cus I’m the King (tube) of wishful thinking. Clinical Question: Is using a small adult BVM during resuscitation of out of hospital cardiac arrest associated with return of spontaneous circulation? Reference: Snyder BD, Van Dyke MR, Walker RG, et al. Association of small adult ventilation bags with return of spontaneous circulation in out of hospital cardiac arrest. Resuscitation 2023. Population: Adult patients treated with an advanced airway for non-traumatic OHCA in a single urban EMS system in the US between 2015 and 2021 Excluded: "Age <18, received basic life support (BLS) only, termination of resuscitation due to advance directives, ALS interventions prior to EMS arrival, insufficient capnography data, cricothyrotomy, advanced airway placed while patient had spontaneous circulation, airway was managed with BVM only, or did not receive CPR while under EMS ALS care.” Exposure: Small bag ventilation with a Mercury Medical CPR-2 Comparison: Large bag ventilation with unspecified “large” BVM Outcome: Primary Outcome: Return of spontaneous circulation (ROSC) at the end of EMS care. This was defined as the time point when the EMS crew entered the receiving ED or termination of resuscitation in the field. Secondary Outcomes: Ventilation rate and mean end-tidal CO2 (ETCO2) value during CPR Type of Study: Retrospective, observational cohort analysis of two prospectively acquired registries managed by one institution’s quality improvement staff. Authors’ Conclusions: “Use of small adult ventilation bags was associated with a lower likelihood of ROSC at the end of EMS care in non-traumatic, adult OHCA.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Yes Was the outcome accurately measured to minimize bias? Yes Have the authors identified all-important confounding factors? Unsure Was the follow up of subjects complete enough? Yes How precise are the results? Precise enough Do you believe the results? Yes Can the results be applied to the local population? Yes Do the results of this study fit with other available evidence? No Funding of the Study. No External Funding. Several authors reported some COIs. Results: There were 3,252 patients who resuscitation attempted during the study period (1,099 large BVM and 2,034 small BVM). Of those, 1,994 met inclusion criteria and were analyzed (663 large bag and 1,331 small bag). The mean age was 61.7 years, 35% female and mean duration of resuscitation was 34 minutes. Both cohorts were reasonably matched except for bystander CPR, public arrests, use of iGels, and interval from 911 call to start of EMS CPR. Key Results: The incidence of ROSC on hospital arrival was significantly lower if the small bags were used versus when large bags were used. Primary Outcome: ROSC was 33% for small bag vs 40% for large. This gave an adjusted odds ratio [aOR] 0.74, 95% CI; 0.61–0.90, p<0.003. Secondary Outcomes: Ventilation rates of breaths/min were not statistically different between small bag and large bag groups ETCO2 was higher in the small bag cohort 36.9 mmHg vs the large bag cohort (33.2 mmHg) p < 0.01 They also listed in Table 2 some other outcomes like survival to admission, which was statistically greater in the large bag cohort, and no statistical difference in survival to discharge or good neurologic function. The authors also conducted sensitivity and exploratory analyses to control for various potential cofounders, but the results were consistent, small bags were associated with lower ROSC rates. 1. Actual Tidal Volumes: This study is based on the hypothesis that hyperventilation of cardiac arrest patients is bad, and that using smaller bags would deliver lower tidal volumes and subsequently lower minute ventilation. We know from their data that there was a wide distribution in the ventilatory rate during CPR ranging from 6-18 breaths per minute in roughly 85% of cases. The mean ventilation rate was 12 breaths per minute in both groups. However, we don’t know how much volume was being delivered with each breath. While it is plausible that use of a smaller bag will lead to lower minute ventilation, at present it is very complicated to measure the actual delivered tidal volumes during OHCA. 2. Measured and Unmeasured Cofounders: They measured several potential confounders in this study. They found there was a four times increase in use of iGel in the small bag group (2% vs 8%), though we can’t attribute that trend to anything specific. The authors did numerous sensitivity analysis to attempt to control forconfounds including medical etiology, public arrest location, time interval from 911 call to initiation of CPR by EMS, total epinephrine dose received, and time interval from 911 call to advanced airway placement. Even when they controlled for all these variables, the association between small bag size and lower odds of ROSC on hospital arrival remained (OR 0.79, 95% CI=0.62–0.99). The study also spanned the onset of the COVID-19 pandemic which undoubtedly changed EMS practice in numerous ways both measurable and unmeasurable. The authors did perform a sensitivity analysis including only pre-covid small-bag patients and the small bags were still inferior. What the authors cannot control for is any unmeasured confounders. 3. Generalizability: This study was obviously not masked. The EMS providers knew what type of bag was being used (small or large). The study also took place in a high performing system that is accustomed to rigorous QA of all cardiac arrest calls. Also, over 90% of patients in each arm of this study were intubated. Intubation is becoming less common as the first line management strategy for OHCA, and some EMS systems may not perform endotracheal intubation at all. This has potential implications for the generalizability of the findings. 4. Retrospectoscope: This is a retrospective study spanning six years. Things change over time, often in ways that are difficult to directly measure. A head-to-head RCT would be a more ideal way to compare a novel strategy to the existing standard. 5. Real World vs Theory: This study is the first real-world investigation of a small-bag strategy for OHCA resuscitation. The evidence supporting the use of smaller BVMs was derived predominately form animal studies. Physiologically it makes sense that hyperventilation could be detrimental in resuscitation, but here in-vivo the standard BVMs (large) was observed to be superior to a small bag. Dr.