Remembering the classics: URI and laryngospasm
Mark Schreiner MD
I started my residency and fellowships in anesthesiology, pediatric anesthesiology, and critical care medicine in the late 1970s. A recurrent question that bedeviled practitioners back then and is still of concern to many today was how, or really if, children with a recent URI should be anesthetized. Although, the answer to this question is fairly well established today,1-3 it is still often debated internally in many of your practices and nationally at annual pediatric anesthesia meetings. The path to figuring out a lot of this was blazed by pioneers in our specialty, perhaps most importantly by the faculty at the University of Michigan4-6 and at the Children’s Hospital of Philadelphia.7 I asked Dr. Mark Schreiner to review his classic paper7 in a remembering the classics PAAD and give us insight into how he and his colleagues went about studying this issue. The lessons learned are as valuable today as they were when he led his team in the 1990s. Myron Yaster MD
Original article
Schreiner MS, O'Hara I, Markakis DA, Politis GD. Do children who experience laryngospasm have an increased risk of upper respiratory tract infection? Anesthesiology. 1996 Sep;85(3):475-80. PMID: 8853076.
In the 1990s, I became interested in whether or not children with a URI or recent URI were more at risk for respiratory complications than “healthy” children, a question that is still of interest today. Unfortunately (from a study design perspective), respiratory complications of potential significance were relatively uncommon. One way to approach rare events is to employ a case-control methodology. Instead of following healthy children with and without a current or recent URI (the potential risk factors) forward in time – during their intra-op and post-op course) to see how many eventually develop a complication, in a case-control study, everyone with the outcome of interest is identified and then one looks backward to see if those with the outcome has one or more of the potential risk factors.8,9
Using this approach, we interviewed each child’s parents in the Day Surgery preoperative waiting area and used the criteria of Tait and Knight5 to determine if the child had an active or recent URI (within 2 weeks) and we also asked the parent for their opinion as to whether or not their child had a URI today or had recently had a URI. Based on the incidence of the various likely respiratory complications in our ORs, we decided to focus just on laryngospasm, since wheezing and other complications were much less common (~1/10th the frequency). Based on a URI prevalence of 15%, a sample size of 123 episodes of laryngospasm was determined sufficient to provide an 80% power to detect a doubling of risk with a type I error rate of 5%.
The important decisions for a case-control study include 1) the choice of control group, 2) ensuring the completeness of the historical record to identify risk factors and 3) ensuring unambiguous definitions for the outcomes of interest. Four children having surgery on the same day, the day before or the day after those who experienced laryngospasm served as the control group. (When cases are uncommon, adding more than one control for each case increases the power of the study but beyond 3 or 4 controls per case, little benefit is accrued.) For the purposes of this study, a uniform operational definition for laryngospasm was employed and each event was adjudicated by one of the investigators. Lastly, to ensure the completeness of the medical record, 15,183 parents provided a history of active or recent URI so that the data was available for the cases and the controls.
Four factors proved significant related to laryngospasm: if a parent thought their child had an active URI (OR 2.05), older age vs younger age as a continuous variable (OR 0.92), those undergoing an airway procedure (OR 2.08) and cases where the anesthetic was overseen by a less experienced anesthesiologist (in first year post-residency training, OR 1.69). Recent URI and URI using Tait and Knight’s criteria were not related to the development of laryngospasm. Since this was a case-control study, the association is be stated backwards compared to a cohort study; i.e., those who had laryngospasm were at increased risk of having an active URI as defined by a parent, not the other way around.
During the study, 143 children experienced laryngospasm, 123 of whom had complete records and 29 of whom had an active URI as defined by a parent. Since having an active URI doubled the risk, extrapolating to the entire cohort, this meant that 2000 cases would have had to be cancelled to prevent 15 cases of laryngospasm. The impact on parents, the OR and children in need of surgery from that many cancellations is obvious.
Some reflections
To have clinical relevance, outcome variables of interest need to be associated with either differences in mortality or morbidity, or impact on quality of life or economics. Laryngospasm is treatable as are wheezing, coughing, and the other minor complications potentially associated with a URI. And with experience, some of these complications can be interrupted early and prevented.
Since our study was conducted prior to introduction of sevoflurane and propofol, it is conceivable that the incidence of laryngospasm and other respiratory complications are even lower now compared to the halothane era. Either huge databases will need to be employed or case-control study methods used to identify differences involving relatively rare events.
I was unaware of any case-control studies in the anesthesia literature before conducting this study but interestingly, in the same issue of Anesthesiology there was another case control study from the Mayo Clinic.10 We subsequently employed a case-control methodology to demonstrate that those with bronchospasm were more likely to have received rapacuronium versus another muscle relaxant (OR =10.1); the data when shard with FDA, helped lead to the removal of rapacuronium from the market.11
Send your thoughts and comments to Myron who will post in a Friday Reader response.
References
1. Hii J, Templeton TW, Sommerfield D, Sommerfield A, Matava CT, von Ungern-Sternberg BS: Risk assessment and optimization strategies to reduce perioperative respiratory adverse events in pediatric anesthesia-Part 1 patient and surgical factors. Paediatr Anaesth 2022; 32: 209-216
2. Templeton TW, Sommerfield D, Hii J, Sommerfield A, Matava CT, von Ungern-Sternberg BS: Risk assessment and optimization strategies to reduce perioperative respiratory adverse events in Pediatric Anesthesia-Part 2: Anesthesia-related risk and treatment options. Paediatr Anaesth 2022; 32: 217-227
3. Regli A, Becke K, von Ungern-Sternberg BS: An update on the perioperative management of children with upper respiratory tract infections. Curr Opin Anaesthesiol 2017; 30: 362-367
4. Tait AR, Knight PR: The effects of general anesthesia on upper respiratory tract infections in children. Anesthesiology 1987; 67: 930-935
5. Tait AR, Knight PR: Intraoperative respiratory complications in patients with upper respiratory tract infections. Can.J.Anaesth. 1987; 34: 300-303
6. Levy L, Pandit UA, Randel GI, Lewis IH, Tait AR: Upper respiratory tract infections and general anaesthesia in children. Peri-operative complications and oxygen saturation. Anaesthesia 1992; 47: 678-682
7. Schreiner MS, O'Hara I, Markakis DA, Politis GD: Do children who experience laryngospasm have an increased risk of upper respiratory tract infection? Anesthesiology 1996; 85: 475-480
8. Schulz KF, Grimes DA: Case-control studies: research in reverse. Lancet. 2002; 359: 431-434
9. Grimes DA, Schulz KF: Compared to what? Finding controls for case-control studies. Lancet. 2005; 365: 1429-1433
10. Warner DO, Warner MA, Barnes RD, Offord KP, Schroeder DR, Gray DT, Yunginger JW: Perioperative respiratory complications in patients with asthma. Anesthesiology 1996; 85: 460-7
11. Rajchert DM, Pasquariello CA, Watcha MF, Schreiner MS: Rapacuronium and the risk of bronchospasm in pediatric patients. Anesth.Analg. 2002; 94: 488-493