Abstract
Background
Fever in children with SARS-CoV-2 infection may increase the risk of intraoperative oxygen desaturation during surgery. This study seeks to find the optimal surgery timing by examining oxygen desaturation rates after fever resolution.
Methods
A prospective cohort study from March to August 2023 included children with SARS-CoV-2 infection who were scheduled for surgery after fever resolution. The primary outcome was the incidence of intraoperative oxygen desaturation. Logistic regression models were used to calculate the adjusted incidence of oxygen desaturation, stratified by time intervals from fever resolution to the day of surgery: 0–2 weeks, 3–4 weeks, 5–6 weeks, 7–8 weeks and ≥3 months.
Results
The intraoperative oxygen desaturation rate was 7.96%. It was highest in the 0–2 weeks group (18.3%), lower in the 3–4 weeks group (11.5%), and further decreased in the 5–6 weeks (6.8%), 7–8 weeks (4.7%) and ≥3 months (4.9%) groups. Adjusted analysis showed significantly higher oxygen desaturation risk in the 0–2 weeks (adjusted OR (aOR), 5.56; 95% CI 3.76 to 8.21) and 3–4 weeks (aOR, 3.31; 95% CI 2.15 to 5.09) groups compared with the ≥3 months group. Risk factors for intraoperative oxygen desaturation included younger age, higher Body Mass Index (BMI), an abnormal chest radiograph and ongoing symptoms (all p<0.05).
Conclusions
To minimise the risk of intraoperative oxygen desaturation, elective surgeries in paediatric patients should be scheduled no earlier than 4 weeks after fever resolution.
Trial registration number
The study was registered at Chinese Clinical Trial Registry http//www.chictr.org.cn/ (Registration date 13/03/23 Trial ID ChiCTR2300069293).
Keywords: COVID-19, Infection Control, Paediatric Lung Disaese, Respiratory Infection
WHAT IS ALREADY KNOWN ON THIS TOPIC
Prior to this study, it was known that children with a SARS-CoV-2 infection were at a higher risk of experiencing adverse respiratory events during surgery, particularly if they had a fever. This is because a fever increases metabolic demand and oxygen requirements, which can lead to complications during surgery. However, there has been a lack of consensus on the optimal timing of surgery following the resolution of fever in these patients.
WHAT THIS STUDY ADDS
This study adds to the existing body of knowledge by identifying a significant association between the timing of surgery after fever resolution and the incidence of intraoperative oxygen desaturation in paediatric patients, and finding that delaying surgery for at least 4 weeks after fever resolution minimises this risk.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The implications of this study are significant for clinical practice, as it provides guidance for scheduling elective surgery in paediatric patients recovering from SARS-CoV-2 infection to reduce the risk of intraoperative oxygen desaturation, and may influence future research, clinical protocols and policy decisions regarding perioperative care in this patient population.
Background
The global spread of SARS-CoV-2 has posed significant challenges to perioperative care for adults and children alike. Many non-urgent operations have been postponed because of the potential risk of perioperative respiratory adverse events (PRAEs). Children with SARS-CoV-2 had a 2.7-fold increased risk of experiencing a drop in oxygen saturation of 10% or more from baseline during airway management compared with controls,1 and retrospective studies have shown that children with SARS-CoV-2 have a higher incidence of PRAEs regardless of the presence of symptoms.2 In 2021, the American Anaesthesiology Association recommended postponing surgery until the SARS-CoV-2 infection had resolved, with a minimum delay of 4 weeks for asymptomatic or mildly symptomatic patients.3 However, another empirical study showed that children with SARS-CoV-2 are less likely to experience PRAEs or die than adults with the virus.4 In recent years, global health guidelines adopted a flexible strategy to adapt to the ongoing presence of SARS-CoV-2, with the aim of mitigating the substantial societal and financial burden resulting from escalated healthcare utilisation, children’s absence from school and parents’ absence from work.5 6 Children with mild symptoms of SARS-CoV-2 who were otherwise healthy could be treated using the same protocols as children with typical upper respiratory tract infections (URTIs).7
Although most children with SARS-CoV-2 experience mild symptoms, surgeons and anaesthetists tend to exercise greater caution when treating children with a fever. Fever is a symptom of infection and an immune response that increases metabolic demand and oxygen requirements, thereby increasing the risk of complications in infected patients undergoing surgery.8 A recent study examining the timing of surgery in paediatric patients recovering from SARS-CoV-2 infection revealed that children with a high fever (>40℃) were at an increased risk of transient blood oxygen desaturation during the post-anaesthesia care unit period.9
Currently, there is a lack of information regarding intraoperative airway complications in children following the resolution of fever. There is also no consensus on the optimal timing of surgery for paediatric patients after fever resolution. Taking advantage of the initial relaxation of pandemic restrictions, we recruited children infected with SARS-CoV-2 who had developed a fever between March and August 2023. The aim of this study was to investigate the association between the timing of surgery and intraoperative oxygen desaturation in these paediatric patients, and to determine the most appropriate timing for surgical intervention.
Methods
Trial design, setting and participants
This prospective cohort study was conducted at a single tertiary care centre (The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University) between 1 March and 31 August 2023. Prior to patient enrolment, the study was registered at www.chictr.org.cn (ChiCTR2300069293). The present study adhered to the guidelines for the reporting of observational studies10 and was conducted in accordance with the Declaration of Helsinki. The trial was approved by the hospital’s Institutional Review Board (IRB No. 2023-K-16-01), and written informed consent was obtained from the parents or legal guardians of all minor subjects. Children aged 8 and above also provided their own assent by signing the consent form alongside their guardians.
This study included paediatric patients with SARS-CoV-2 infection and fever resolution who were scheduled for surgery. Paediatric patients infected with SARS-CoV-2 and who exhibited fever were enrolled based on specific criteria: (a) positive rapid antigen test performed; (b) positive Reverse Transcription-Polymerase Chain Reaction nasopharyngeal swab and (c) history of cohabitation with SARS-CoV-2 positive patients. Fever was defined as an oral temperature ≥37.2°C, rectal temperature ≥37.8°C, or axillary temperature ≥37.5°C,11 tympanic or temporal temperature ≥38.0°C.12 Resolution of fever was determined when the temperature in the respective site fell below these thresholds without subsequent recurrence. The inclusion criteria were: (1) paediatric patients aged 1 to 18 years old; (2) American Society of Anesthesiologists physical status (ASA) I or II; (3) undergoing selective tonsillectomy, nasal and paranasal sinus surgery, inguinal hernia repair, circumcision, internal fixation removal, or other elective or daytime operations in otolaryngology, general surgery or orthopaedics. The exclusion criteria were: (1) for children under 2 years of age: the weight is either less than or more than 15% of standard weight (standard weight (kg)=height (cm) −100), used as a pragmatic screening tool for significant malnutrition or overnutrition in this age group where BMI is not routinely applied; (2) for children aged 2 years and older: BMI <13.5 kg/m2 or >31 kg/m2; (3) presence of asthma or neuromuscular systemic disease or cachexia, or difficult airway; (4) operation duration >2 hours; (5) participants in any medication clinical trial within 30 days before the study; and (6) absence of a definite date of fever recovery. These exclusion criteria were implemented to ensure a more homogeneous cohort of patients undergoing low-to-moderate risk procedures, thereby reducing the potential for confounding by factors other than the primary variable of interest (time since fever resolution).
Clinical protocol and data collection
On the day of the operation, the paediatric anaesthetist responsible for anaesthetising the child will carry out a preoperative assessment to determine the feasibility of general anaesthesia and to classify the patient’s physical condition according to the ASA classification. After obtaining informed consent for anaesthesia, three fixed anaesthetists (preoperative interviewers) assigned to the research team conducted an additional preoperative interview with the children and their guardians in a separate designated room.
The child’s guardian provided the specific date of fever reduction according to the medical records, medicine purchase records and the school leave records. The return to normal body temperature, a key symptom of SARS-CoV-2 infection,13 was considered the beginning of recovery as it is a simple and clear indicator. The time between fever resolution and surgery was recorded as a categorical factor and categorised into several intervals for analysis: 0–2 weeks, 3–4 weeks, 5–6 weeks, 7–8 weeks (the 0–8 weeks group) and ≥3 months (the control group). Three preoperative interviewers recorded any respiratory symptoms other than fever (cough, expectoration, sore throat, stuffy nose, runny nose), and they also noted whether these symptoms have disappeared by the day of the operation. Symptoms were classified as asymptomatic except fever, symptomatic-resolved or symptomatic except fever-ongoing. Additionally, preoperative interviewers collected and documented the findings from preoperative chest radiograph examinations before operation. A chest radiograph was deemed abnormal if it did not explicitly state “no obvious abnormality”. Abnormalities included conditions such as bronchitis, bronchiolitis, altered lung texture, pulmonary opacities, chronic inflammation, patchy density shadows and suspicious linear opacities.
After entering the operating room, the children were routinely monitored for pulse oxygen saturation (SpO2), blood pressure and electrocardiogram. SpO2 was measured using an oximetry probe (M1133A, Philips, India), which was placed on the right index finger. The child’s anaesthetist decides on the method of anaesthesia and the choice of drugs.
Perioperative medication included the preoperative medication such as midazolam, esketamine hydrochloride injection and atropine, as well as intraoperative narcotic medication such as propofol, sevoflurane, fentanyl, remifentanil, ropivacaine hydrochloride injection, cisatracurium and rocuronium bromide injection. We categorised impairments in oxygenation according to SpO2 levels. Oxygen desaturation: any episode in which SpO2 drops below 95%.914,16 Hypoxaemia: a more severe subset of desaturation events, defined as an SpO2 level below 90%. Hypoxaemia was further subclassified by severity: mild hypoxaemia: SpO2 81%–90%; moderate hypoxaemia: SpO2 51%–80%; and severe hypoxaemia: SpO2 ≤50%.17 From the induction of anaesthesia to leaving the operating room, the SpO2 was less than 95%, and an event was recorded. If a child’s SpO2 was recorded as less than 95% on at least one occasion, the case was marked as positive for oxygen desaturation. In instances of oxygen desaturation, anaesthetists intervened to improve oxygenation using various strategies, including suctioning airway secretions, administering supplemental oxygen via a face mask, applying mask-delivered continuous positive airway pressure, inserting an oropharyngeal airway, employing a laryngeal mask airway or performing endotracheal intubation. The duration of the operation was defined as the elapsed time from the start to the completion of the surgical procedure. SARS-CoV-2 symptoms include respiratory manifestations such as cough, sputum production, sore throat, nasal congestion and rhinorrhoea.
Outcomes
The primary outcome was the incidence of intraoperative oxygen desaturation (defined as SpO2 <95%). The secondary outcomes were the identification of independent risk factors associated with intraoperative oxygen desaturation and the severity of intraoperative hypoxaemia, classified as mild (SpO2 81%–90%), moderate (SpO2 51%–80%) or severe (SpO2 ≤50%).
Sample size calculations
Based on prior research,17 the expected oxygen desaturation rate in children with SARS-CoV-2 undergoing tracheal management was 3%–7% within 0–8 weeks after fever resolution, compared with 3% for those waiting ≥3 months. We set the oxygen desaturation rate at 7% for the experimental group (0–8 weeks fever resolution) and 3% for the control group (≥3 months fever resolution). With an alpha level of 0.05 and a power of 80%, the sample size calculation required 425 children per group. Accounting for a 10% dropout rate and dividing the 0–8 weeks period into four intervals (0–2, 3–4, 5–6 and 7–8 weeks), the total estimated sample size for the study was 2362 children.
Statistical analysis
Statistical analysis was carried out by R (version R-4.2.3). Continuous data would be expressed as mean with SD if normally distributed or median with IQR if not. For normally distributed data, analysis of variance (ANOVA) would be applied for multiple groups to compare the means, and Kruskal-Wallis H test would be used if data were not distributed normally. The normality of the data distribution was examined using the Kolmogorov-Smirnov test. Categorical and binary data were presented as frequencies with percentages, and χ² or Fisher’s exact tests were used for comparisons among groups. Univariate and multivariate analyses for the prespecified variables were carried out by using the logistic regression and the unadjusted/adjusted ORs with 95% CIs were calculated. These variables include age, BMI, primary airway device, induction technique, surgical type, duration of operation and respiratory tract infection. To address possible biases further, the average marginal effects were used to produce an adjusted oxygen desaturation incidence rate over time, from body temperature returned to normal to surgery, stratified by the following variables: age (1 to 4 vs 5 to 18 years), chest radiograph (normal vs abnormal), SARS-CoV-2 symptoms (symptomatic vs symptomatic except fever-ongoing), primary airway device (tracheal tube vs laryngeal mask), induction technique (inhalational vs intravenous) and type of surgery (ear-nose throat vs non-ear, nose and throat (ENT)). A two-sided p<0.05 was considered to indicate statistical significance.
Patient and public involvement
There was no patient or public involvement in the design and conduct of the present study.
Results
Demographic characteristics
A total of 3495 patients were initially recruited for the study. Of these, 365 could not provide the exact date of temperature recovery, 69 did not receive airway intervention and 8 patients had their surgery cancelled. A final total of 3053 children were included (figure 1). 427 patients underwent surgery within 0–2 weeks after fever resolution. 443 patients were in the 3–4 weeks group, 438 in the 5–6 weeks group, 428 in the 7–8 weeks group and 1317 in the control group, who received surgery after ≥3 months. The ≥3 months group was significantly younger than 0–8 weeks groups (mean age 5.16 SD (3.31) vs 6.37 SD (3.47) years, p<0.001). The proportion of patients in the younger children (1–4 years old) was also higher in the ≥3 months group (47.8% vs 33.1%). The median BMI was significantly higher in the ≥3 months group than in the 0–8 weeks groups (17.17 IQR (15.44–19.56) vs 16.53 IQR (15.09–18.51), p<0.0001). There was a significant difference in operation type between the ≥3 months group and the 0–8 weeks groups (p=0.003). Detailed information was shown in table 1 and online supplemental table 1.
Figure 1. Study flowchart. ASA, American Society of Anesthesiologist.
Table 1. Baseline characteristics and outcomes for patients stratified by interval from fever resolution to surgery.
| ≥3 months (n=1317) | Time since fever resolution | ||||
|---|---|---|---|---|---|
| 0–2 weeks (n=427) | 3–4 weeks (n=443) | 5–6 weeks (n=438) | 7–8 weeks (n=428) | ||
| Characteristics, no. (%) | |||||
| Sex | |||||
| Male | 954 (72.4) | 318 (74.5) | 320 (72.2) | 300 (68.5) | 314 (73.4) |
| Female | 363 (27.6) | 109 (25.5) | 123 (27.8) | 138 (31.5) | 114 (26.6) |
| Age, years | |||||
| 1–4 | 629 (47.8) | 144 (33.7) | 105 (23.7) | 145 (33.1) | 180 (42.1) |
| 5–12 | 642 (48.7) | 256 (60.0) | 304 (68.6) | 276 (63.0) | 231 (54.0) |
| 13–18 | 46 (3.5) | 27 (6.3) | 34 (7.7) | 17 (3.9) | 17 (4.0) |
| BMI, median (IQR) | 17.17 (15.44, 19.56) | 16.83 (15.28, 18.85) | 16.26 (15.04, 18.55) | 16.57 (15.14, 18.51) | 16.44 (14.98, 18.12) |
| ASA physical status | |||||
| I | 708 (53.8) | 228 (53.4) | 246 (55.5) | 214 (48.9) | 206 (48.1) |
| II | 609 (46.2) | 199 (46.6) | 197 (44.5) | 224 (51.1) | 222 (51.9) |
| Type of operation | |||||
| Ear nose throat branch surgery | 609 (46.2) | 192 (45.0) | 200 (45.1) | 262 (59.8) | 249 (58.2) |
| General surgery | 617 (46.8) | 218 (51.1) | 217 (49.0) | 155 (35.4) | 153 (35.7) |
| Orthopaedic surgery | 91 (6.9) | 17 (4.0) | 26 (5.9) | 21 (4.8) | 26 (6.1) |
| Duration of surgery | |||||
| ≤30 min | 839 (63.8) | 272 (63.8) | 327 (74.0) | 296 (67.7) | 267 (62.4) |
| >30 min | 477 (36.2) | 154 (36.2) | 115 (26.0) | 141 (32.3) | 161 (37.6) |
| Primary airway device | |||||
| Tracheal tube | 738 (56.0) | 227 (53.2) | 216 (48.8) | 265 (60.5) | 254 (59.3) |
| Laryngeal mask | 579 (44.0) | 200 (46.8) | 227 (51.2) | 173 (39.5) | 174 (40.7) |
| Induction technique | |||||
| Inhalational | 164 (12.5) | 40 (9.4) | 31 (7.0) | 36 (8.2) | 22 (5.1) |
| Intravenous | 1153 (87.5) | 387 (90.6) | 412 (93.0) | 402 (91.8) | 406 (94.9) |
| SARS-CoV-2 symptoms | |||||
| Asymptomatic except fever | 754 (57.4) | 253 (59.3) | 208 (47.0) | 221 (50.5) | 270 (63.1) |
| Symptomatic-resolved | 471 (35.8) | 165 (38.6) | 211 (47.6) | 198 (45.2) | 146 (34.1) |
| Symptomatic except fever-ongoing | 89 (6.8) | 9 (2.1) | 24 (5.4) | 19 (4.3) | 12 (2.8) |
| Abnormal chest radiograph | 110 (8.4) | 37 (8.7) | 40 (9.0) | 34 (7.8) | 25 (5.8) |
| Incidence of intraoperative oxygen desaturation | 64 (4.9) | 78 (18.3) | 51 (11.5) | 30 (6.8) | 20 (4.7) |
| Perioperative medication | |||||
| Propofol | 1151 (87.4) | 386 (90.4) | 411 (92.8) | 400 (91.3) | 404 (94.4) |
| Fentanyl | 1009 (76.6) | 305 (71.4) | 352 (79.5) | 341 (77.9) | 349 (81.5) |
| Remifentanil | 166 (12.6) | 64 (15.0) | 60 (13.5) | 63 (14.4) | 58 (13.6) |
| Sevoflurane | 1235 (93.8) | 389 (91.1) | 420 (94.8) | 406 (92.7) | 402 (93.9) |
| Atropine | 87 (6.6) | 25 (5.9) | 19 (4.3) | 34 (7.8) | 35 (8.2) |
| Esketamine hydrochloride injection | 74 (5.6) | 17 (4.0) | 15 (3.4) | 5 (1.1) | 7 (1.6) |
| Ropivacaine hydrochloride injection | 248 (18.8) | 79 (18.5) | 88 (19.9) | 67 (15.3) | 68 (15.9) |
| Cisatracurium | 276 (21.0) | 46 (10.8) | 23 (5.2) | 21 (4.8) | 24 (5.6) |
| Rocuronium bromide injection | 109 (8.3) | 62 (14.5) | 87 (19.6) | 62 (14.2) | 91 (21.3) |
| Midazolam | 78 (5.9) | 15 (3.5) | 6 (1.4) | 17 (3.9) | 11 (2.6) |
ASA, American Society of Anesthesiologists status; BMI, Body Mass Index is calculated as weight in kilograms divided by height in metres squared; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
The incidence of oxygen desaturation
Overall, the rate of intraoperative oxygen desaturation was 7.96% (243/3053). The incidence of oxygen desaturation was 18.3% (78/427) in 0–2 weeks, 11.5% (51/443) in 3–4 weeks, 6.8% (30/438) in 5–6 weeks, 4.7% (20/428) in 7–8 weeks and 4.9% (64/1318) in ≥3 months. In the adjusted model, compared with the children in the ≥3 months group, children in the 0–2 weeks (adjusted OR (aOR), 5.56; 95% CI 3.76 to 8.21, p<0.001) and 3–4 weeks (aOR, 3.31; 95% CI 2.15 to 5.09, p<0.001) groups had a significantly higher risk of intraoperative oxygen desaturation incidence. However, there were no significant differences in the incidence of intraoperative oxygen desaturation between the 5–6 weeks (aOR, 1.46; 95% CI 0.9 to 2.37) and 7–8 weeks groups (aOR, 1.07; 95% CI 0.62 to 1.84) (table 2). These findings were also consistent across subgroups stratified by age, chest radiograph, SARS-CoV-2 symptoms, primary airway device, induction technique and type of surgery (online supplemental table 2 and figure 2).
Table 2. Unadjusted and adjusted models of perioperative oxygen desaturation incidence in all patients.
| Unadjusted | Adjusted | |||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Sex | ||||
| Female vs male | 0.78 (0.57 to 1.07) | 0.12 | 0.8 (0.57 to 1.12) | 0.19 |
| Age | ||||
| 1–4 | Ref | – | Ref | – |
| 5–12 | 0.84 (0.64 to 1.10) | 0.208 | 0.6 (0.44 to 0.81) | 0.001 |
| 13–18 | 0.87 (0.45 to 1.66) | 0.662 | 0.37 (0.18 to 0.77) | 0.008 |
| BMI | 1.1 (1.06 to 1.14) | <0.001 | 1.13 (1.09 to 1.18) | <0 .001 |
| ASA physical status | ||||
| II vs I | 1.33 (1.02 to 1.74) | 0.036 | 0.64 (0.35 to 1.16) | 0.139 |
| Type of operation | ||||
| Ear nose throat branch surgery | Ref | – | Ref | – |
| General surgery | 0.70 (0.53 to 0.93) | 0.013 | 0.55 (0.29 to 1.04) | 0.067 |
| Orthopaedic surgery | 0.69 (0.38 to 1.28) | 0.239 | 0.85 (0.36 to 1.98) | 0.701 |
| Duration of surgery | ||||
| >30 vs ≤30 min | 0.92 (0.69 to 1.22) | 0.557 | 0.9972 (0.73 to 1.37) | 0.986 |
| Primary airway device | ||||
| Laryngeal mask vs tracheal tube | 0.65 (0.49 to 0.86) | 0.002 | 0.57 (0.34 to 0.94) | 0.028 |
| Induction technique | ||||
| Intravenous vs inhalational | 1.59 (0.93 to 2.72) | 0.093 | 1.82 (0.20 to 16.23) | 0.593 |
| SARS-CoV-2 symptoms | ||||
| Asymptomatic except fever | Ref | – | Ref | – |
| Symptomatic-resolved | 1.24 (0.94 to 1.64) | 0.13 | 1.19 (0.88 to 1.59) | 0.26 |
| Symptomatic except fever-ongoing | 1.84 (1.08 to 3.12) | 0.024 | 2.18 (1.24 to 3.83) | 0.007 |
| Chest radiograph | ||||
| Abnormal vs normal | 3.33 (2.34 to 4.74) | <0.001 | 3.22 (2.20 to 4.71) | <0.001 |
| Perioperative medication | ||||
| Propofol | 1.52 (0.9 to 2.57) | 0.114 | 0.80 (0.10 to 6.73) | 0.838 |
| Fentanyl | 1.13 (0.81 to 1.58) | 0.464 | 1.13 (0.77 to 1.67) | 0.528 |
| Remifentanil | 1.32 (0.92 to 1.88) | 0.132 | 1.18 (0.78 to 1.78) | 0.437 |
| Sevoflurane | 1.31 (0.66 to 2.61) | 0.443 | 0.10 (0.46 to 2.17) | 0.994 |
| Atropine | 0.47 (0.23 to 0.97) | 0.041 | 0.47 (0.22 to 1.00) | 0.05 |
| Esketamine hydrochloride injection | 0.41 (0.15 to 1.11) | 0.079 | 0.45 (0.16 to 1.28) | 0.135 |
| Ropivacaine hydrochloride injection | 0.77 (0.53 to 1.13) | 0.189 | 0.93 (0.60 to 1.43) | 0.726 |
| Cisatracurium | 0.92 (0.61 to 1.39) | 0.696 | 0.96 (0.59 to 1.57) | 0.874 |
| Rocuronium bromide injection | 0.89 (0.59 to 1.33) | 0.560 | 0.93 (0.59 to 1.48) | 0.768 |
| Midazolam | 1.37 (0.76 to 2.48) | 0.294 | 1.46 (0.77 to 2.76) | 0.246 |
| Group | ||||
| ≥3 months | Ref | – | Ref | – |
| 0–2 weeks | 4.31 (3.00 to 6.18) | <0.001 | 5.56 (3.76 to 8.21) | <0.001 |
| 3–4 weeks | 2.46 (1.66 to 3.63) | <0.001 | 3.31 (2.15 to 5.09) | <0.001 |
| 5–6 weeks | 1.34 (0.85 to 2.12) | 0.206 | 1.46 (0.90 to 2.37) | 0.127 |
| 7–8 weeks | 0.93 (0.55 to 1.56) | 0.772 | 1.07 (0.62 to 1.84) | 0.807 |
The value is OR (95% CI).
ASA, American Society of Anesthesiologists status; BMI, Body Mass Index is calculated as weight in kilograms divided by height in metres squared; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Figure 2. Risk of oxygen desaturation during paediatric surgery by time since fever resolution. (A) Entire population. (B) Stratified by age groups. (C) Stratified by chest radiograph results. (D) Stratified by induction method. (E) Stratified by SARS-CoV-2 symptoms. (F) Stratified by type of surgery. (G) Stratified by primary airway device.
The risk factors of oxygen desaturation
Multivariate logistic regression showed that younger age (1–4 years old), higher BMI, symptomatic except fever-ongoing and abnormal chest radiograph were the risk factors of oxygen desaturation during operation (all p<0.05). However, laryngeal mask airway (p=0.028) and atropine (p=0.050) were more conducive to reducing intraoperative oxygen desaturation (table 2).
The severity of hypoxaemia
There were significant differences in the severity of intraoperative hypoxaemia based on the timing since recovery from fever. The severe hypoxaemia (≤50%) was rare, occurring in only a few cases across all groups, with no significant difference noted (p=0.557). Moderate hypoxaemia (51%–80%) showed an increasing trend as the time since recovery from fever decreased, with the highest incidence in the 0–2 weeks group at 2.8% and the lowest in the 7–8 weeks group at 0.7% (p=0.014). There was no significant difference in the incidence of mild hypoxaemia (81%–90%) compared with the other groups (p=0.092) (table 3).
Table 3. Severity of intraoperative oxygen desaturation in children by time since fever resolution.
| Severity of intraoperative oxygen desaturation (SpO2%) | ≥3 months (n=1317) | 0–2 weeks (n=427) | 3–4 weeks (n=443) | 5–6 weeks (n=438) | 7–8 weeks (n=428) | P value |
|---|---|---|---|---|---|---|
| Severe hypoxaemia | 3 (0.2) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.2) | 0.5573 |
| Moderate hypoxaemia | 11 (0.8) | 12 (2.8) | 5 (1.1) | 4 (0.9) | 3 (0.7) | 0.0139 |
| Mild hypoxaemia | 35 (2.7) | 19 (4.4) | 19 (4.3) | 12 (2.7) | 8 (1.9) | 0.0921 |
| Oxygen desaturation | 58 (4.4) | 75 (17.6) | 50 (11.3) | 29 (6.6) | 19 (4.4) | <0.0001 |
| Normal | 1259 (95.6) | 352 (82.4) | 392 (88.5) | 406 (92.7) | 401 (93.7) | <0.0001 |
Severe hypoxaemia: SpO2 ≤50%; moderate hypoxaemia: SpO2 51%–80%; mild hypoxaemia: SpO2 81%–90%; oxygen desaturation: <95%; normal: 95%–100%.
SpO2, pulse oxygen saturation.
Discussion
In paediatrics, a saturation level below 95% clearly falls outside the normal range and serves as a highly sensitive early indicator of respiratory compromise. This study reveals a significant association between the interval from fever resolution to surgery and the incidence of intraoperative oxygen desaturation (SpO2 <95%) in paediatric patients with a recent SARS-CoV-2 infection. Our analysis demonstrates that the risk of oxygen desaturation decreased as the duration after fever resolution lengthened. Specifically, patients who underwent surgery within 0–2 weeks or 3–4 weeks post-fever exhibited a notably higher incidence of oxygen desaturation compared with those who had recovered for 5–6 weeks, 7–8 weeks and ≥3 months. These findings underscore that deferring elective surgery for at least 4 weeks after fever resolution is critical for mitigating perioperative oxygen desaturation risk in this population.
Younger age, obesity, duration of anaesthesia and symptoms of URTIs have been identified as independent risk factors for intraoperative oxygen desaturation in children undergoing general anaesthesia,18 19 particularly in infants under 1 year of age.20 A randomised controlled trial showed that the incidence of PRAEs was significantly lower in infants undergoing minor surgery with a laryngeal mask airway compared with tracheal intubation.21 The use of a laryngeal mask airway has been found to be safer than tracheal intubation in paediatric surgery,22,24 which is broadly consistent with our findings. All children were extubated under deep anaesthesia. Studies have shown that deep extubation or laryngeal mask removal can be performed by an experienced paediatric anaesthetist without increasing the risk of desaturation.25 26 In addition, the study found that abnormal chest radiographs indicated a higher risk of intraoperative oxygen desaturation. However, the studies found no association between oxygen desaturation and the type of surgery or induction technique. This difference could be due to the fact that we specifically included outpatient and elective minor procedures, which inherently have a more homogeneous and lower risk profile. Consequently, our findings are most applicable to these common, low-risk procedures (eg, tonsillectomy, hernia repair). For this specific category of surgery, the dilemma of scheduling timing after SARS-CoV-2 infection is most prevalent, as there is a greater clinical willingness to proceed compared with major, high-risk operations. Importantly, there were differences in some baseline characteristics between the groups, notably a higher proportion of younger children and a different mix of surgical cases. This is an inherent challenge in observational studies where the timing of surgery is not randomised. As a younger age is a recognised risk factor for adverse respiratory events during surgery, the higher prevalence of this risk factor in the ≥3 months control group may have led to an underestimation of the true protective effect of delaying surgery in the unadjusted analysis. However, our multivariate logistic regression model, which controlled for age, BMI, surgical type and other potential confounders, demonstrated that the interval from fever resolution to surgery was still a strong independent predictor of oxygen desaturation. The persistence of a significantly elevated risk in the 0–4 week groups after adjustment, coupled with consistent findings across subgroups stratified by age and surgical type, highlights that the timing of surgery is a dominant, modifiable risk factor that overrides the influence of these underlying patient characteristics.
The guidelines by El-Boghdadly et al27 recommend that elective surgery for SARS-CoV-2 infection should be delayed at least 7 weeks after infection, unless the benefits outweigh the risks of waiting. This advice was based on evidence that SARS-CoV-2 infection was associated with an increased incidence of perioperative adverse events and mortality, particularly in the first 6 weeks. However, the guidelines did not recommend the timing of surgery for children with SARS-CoV-2 infection. The research by Geng-Ramos et al28 showed that the incidence of postoperative complications increased significantly after children underwent surgery under general anaesthesia within 7 days of SARS-CoV-2 diagnosis. This was consistent with the research of Petersen et al,17 who reported an increased risk of overall complications and hypoxaemia during airway management in paediatric patients suspected or diagnosed with SARS-CoV-2 under general anaesthesia. According to a prospective cohort study, the incidence of PRAEs in children with URTIs symptoms increased significantly in the 2 weeks before surgery but decreased significantly in the 2–4 weeks before surgery.15 A recent review supported delaying surgery for 2 weeks after resolution of URTIs symptoms without complications and for 4 weeks after the occurrence of severe URTIs symptoms (such as fever),6 which is similar to our research findings that the incidence of intraoperative oxygen desaturation in asymptomatic children on the day of surgery was relatively low, regardless of the presence of URTIs symptoms during fever.
In our study, the overall incidence of intraoperative oxygen desaturation (SpO2 <95%) decreased significantly with longer intervals after fever resolution. Although the occurrence of severe hypoxaemia (SpO2 ≤50%) was rare and did not differ statistically between groups, it is noteworthy that three of the four observed cases occurred in the ≥3 months group. Among these, two patients were asymptomatic on the day of surgery, and two exhibited normal chest radiograph findings. This suggests that intraoperative hypoxaemia may be influenced by a multifactorial interplay. Consequently, hypoxaemia risk cannot be predicted solely based on the time since fever resolution, symptomatic status or radiographic findings. We emphasise that the role of anaesthetist expertise is particularly critical in such scenarios. All anaesthetists involved in this study were specifically trained in paediatric anaesthesia and possessed over a decade of clinical experience. As supported by previous literature,18 29 skilled perioperative management—including comprehensive risk assessment, adept handling of respiratory adverse events and tailored anaesthetic protocols—can substantially mitigate intraoperative risks. This may explain the low overall rate of severe complications observed, even among children with a recent SARS-CoV-2 infection. It also highlights the importance of experienced anaesthetic care for safe paediatric anaesthesia, particularly for those at risk of potential respiratory compromise.
This study has several limitations. First, the single-centre design and the specific time period of recruitment (following the widespread surge of SARS-CoV-2 after the relaxation of control measures) may affect the generalisability of our findings, and validation through future multicentre studies is warranted. Second, rather than including a cohort of children without perioperative SARS-CoV-2 infection, we used children who had been afebrile for ≥3 months as the control group—a pragmatic decision given the context of near-population-level exposure during the study period. While multivariate adjustment and subgroup analyses were employed to address baseline differences, the possibility of residual confounding cannot be fully excluded. Additionally, the inclusion of children based on household exposure rather than a confirmed positive test may have introduced a small degree of misclassification bias. It is important to note that during the study period, following the relaxation of epidemic prevention and control policies in China, there was an unprecedented surge of SARS-CoV-2 infections. Within this specific epidemiological context, the combination of fever and known household exposure was considered a clinically robust and pragmatically justified indicator of SARS-CoV-2 infection. Finally, data on individual vaccination status were not collected. However, during the study period, a complete two-dose vaccination was mandatory for school attendance in China, resulting in near-universal coverage in children aged ≥3.5 years. As the potential for being unvaccinated was effectively confined to the youngest children, and since younger age was itself a significant risk factor in our analysis, we expect that the impact of this unmeasured variable on our primary conclusions is minimal.
Conclusion
In this study, for children recovering from SARS-CoV-2 infection, it is recommended that elective surgeries be scheduled no earlier than 4 weeks after fever resolution to mitigate the risk of intraoperative oxygen desaturation, unless the potential benefits of earlier surgery are deemed to surpass the associated risks. Comprehensive perioperative risk assessment and meticulous optimisation of perioperative anaesthesia management are crucial for balancing the urgency of surgical needs against the potential risks of intraoperative oxygen desaturation and other complications.
Supplementary material
Acknowledgements
We extend our sincere thanks to all the physicians, postgraduates and nurses in the Department of Anesthesiology and Perioperative Medicine at the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University for their invaluable assistance and cooperation in this study. Their contributions were pivotal to the smooth progress and successful completion of our research.
Footnotes
Funding: This work was supported by the Zhejiang Provincial Health Commission (grant number 2022KY208) and Wenzhou basic scientific research project (grant number Y20220308).
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Consent obtained from parent(s)/guardian(s).
Ethics approval: The trial was approved by The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University’s Institutional Review Board (IRB No. 2023-K-16-01). Participants gave informed consent to participate in the study before taking part.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
All data relevant to the study are included in the article or uploaded as supplementary information.