Safety of Seasonal Influenza Vaccination in Hospitalized Surgical Patients
Venue: Annals of Internal Medicine

Vaccination against influenza is recommended before discharge for surgical inpatients who have not yet been vaccinated. Vaccination rates are low in this population, perhaps due to concerns that adverse effects of the vaccine, such as fever and myalgia, could be confused with surgical complications.  In an integrated health care system, no differences were found in inpatient or emergency department visits, postdischarge fever, or clinical evaluations for infection in surgical patients who received the influenza vaccine versus those who did not.  A policy of influenza vaccination before hospital discharge seems to be clinically appropriate for surgical patients. Yearly mortality due to influenza infection in the United States fluctuates considerably, ranging from about 3000 deaths to about 49000 deaths between the 19761977 and 20062007 influenza seasons (1, 2) Children are at greatest risk for infection, but rates of serious complications and death are highest among persons older than 65 years and those with certain underlying health conditions (3, 4) Influenza vaccination is the primary method for preventing the illness and its severe complications, and annual vaccination is recommended for all persons aged 6 months or older (5) All health care contacts, including hospitalizations, provide excellent opportunities for vaccination, particularly for persons at the highest risk for complications and death from influenza. The Advisory Committee on Immunization Practices currently recommends that eligible hospitalized patients receive the influenza vaccine before discharge (6) This preventive strategy is measured in quality metrics of inpatient immunization by the Joint Commission and the Centers for Medicare Medicaid Services. However, missed opportunities to vaccinate eligible inpatients persist. Persons who are hospitalized for surgical procedures are often not targeted for vaccination. This may be due to perceptions about the safety of vaccination held by patients, family members, and providers. Among surgeons, there are concerns that potential adverse effects of influenza vaccinations that develop in the perioperative period, including fever (3.3% of patients) and myalgia (3.12% of patients) (7) could instead be attributed to surgical complications. A survey of pediatric anesthetists found that most respondents recommended postponing elective surgery by 1 to 6 weeks after vaccination (8) Thus, the concern among providers is that vaccine associated adverse events could lead to unnecessary evaluations and would influence postsurgical care. Specifically, postsurgical vaccine associated fever or myalgia could be erroneously attributed to an infectious complication of the surgery. The uncertainty in attribution of fever can affect decision making during recovery and may reflect poorly on surgical performance by inflating postsurgical complication rates. Although this concern is understandable, few clinical data support it. We were able to identify only 2 studies evaluating the safety of influenza vaccination in hospitalized patients (9, 10) These studies confirmed the safety and immunogenicity of the vaccine in hospitalized patients and also found that one of the most common reasons physicians gave for not ordering vaccination before discharge was that patients were not stable enough to be vaccinated before discharge (9, 10) We were not able to identify any studies investigating potential increased risk for complications associated with perioperative vaccination. To provide clinical evidence that would either substantiate or refute concerns about the safety of perioperative vaccination, we conducted a study to describe influenza vaccination during inpatient stays for surgery and to evaluate whether vaccination that occurs during that period increases health care utilization after discharge, including postsurgical infection work ups. The results of this study fill a gap in available clinical data to inform current vaccine recommendations for surgical inpatients by providing a real world assessment of the effect of vaccination in the perioperative period.  The study included prepaid health plan members of the Kaiser Permanente Southern California (KPSC) health care system. The KPSC system has 4.0 million members who are representative of the socioeconomic and racial diversity of the population of the area (11) It uses electronic health records to integrate medical information, such as diagnostic, immunization, medication, and procedure codes as well as laboratory results from all outpatient, emergency department (ED) and hospital visits. Minimal copayments are a strong incentive to receive care within the KPSC system. All recommended immunizations are free to members regardless of copayment status. All 14 hospitals in the KPSC region have inpatient services and were included in this study.  In this retrospective cohort study, all KPSC patients who were aged 6 months or older; had inpatient surgery identified by a procedure code from the International Classification of Diseases, Ninth Revision >2400 codes [available upon request] and were eligible for an influenza vaccination in any of the 3 influenza seasons from 2010 to 2013 were included. Influenza seasons were defined as starting on 1 September and ending on 31 March. Continuous enrollment was required from 6 months before the date of surgery (allowing a 31 day gap for administrative delays in membership renewal) or from 1 September of the influenza season in which the surgery was performed, whichever was longer. Enrollment was also required through 7 days after discharge. Patients who were ineligible for vaccination during their surgical hospitalization, including those who received a bone marrow transplant within 6 months before surgery and those with an allergy to the influenza vaccine or eggs, were excluded from the study cohort. For each patient, only the first surgery occurring between September and March of each influenza season was included in the analyses. The protocol for this study was reviewed and approved by the KPSC Institutional Review Board, which waived the requirement for informed consent.  The primary outcomes for this study included rates of outpatient visits, readmission, or ED visits in the 7 days after discharge. In addition, rates of infection related outcomes, such as fever (defined as temperature 38.0C) and clinical laboratory work ups for infection (urine culture, complete blood count, blood culture, and wound culture) during the 7 days after discharge were assessed. Exposure and Covariates All influenza vaccinations administered to patients in the study cohort between 1 August and 30 April in the 20102011, 20112012, and 20122013 influenza seasons were identified. Data on age (6 months to 5 years, 6 to 17 years, 18 to 49 years, 50 to 64 years, 65 to 84 years, and 85 years) sex (male or female) race/ethnicity (Hispanic; white; African American; Asian; or multiple, other, or unknown) surgery type (cardiac; eye; neurosurgery; general surgery; dermatologic; ear, nose, and throat; obstetrics and gynecology; oral and maxillofacial; orthopedics; plastics; podiatric; urologic; or vascular) health care utilization in the 6 months before surgery (for example, the number of outpatient visits, ED visits, and hospitalizations) calendar month, influenza season (20102011, 20112012, or 20122013) medical center (n= 13) and comorbidity score (Charlson Comorbidity Index score for patients aged 18 years and Rhee pediatric surgical risk score  for those aged <18 years, assessed during the 6 months before surgery) were also collected for all participants.  Vaccination and Surgery Descriptive analyses included calculations of the proportions of influenza vaccinations by time frame to describe the timing of vaccination relative to the surgical inpatient stay in the cohort. Proportions were further stratified by patient demographic characteristics, calendar month, influenza season, medical center, and surgery type. When timing categories overlapped (for example, admission, surgery, and discharge occurred on the same day) the vaccination was attributed to the day of the surgery. The numerator for these proportions was the number of vaccinations in the period of interest, and the denominator was the total number of surgeries over all periods during the influenza season. Statistical Analysis Statistical analyses evaluated whether the risk for the outcomes of interest differed by influenza vaccination status. The exposed group was defined as patients who received influenza vaccination during their inpatient stay. The unexposed group was defined as those who were unvaccinated during that influenza season or were vaccinated more than 7 days after discharge. We used propensity score analyses with inverse probability of treatment weighting (IPTW) to adjust for confounding by characteristics, which predicted the likelihood that vaccination was associated with risk for surgical complications. First, we used a logistic regression model to estimate the probability of exposure, as predicted by age at surgery, sex, race/ethnicity, surgery type, health care utilization, calendar month, influenza season, length of stay, medical center, and comorbidity score. Second, the weight for each patient was calculated as the inverse of their predicted probability of exposure and was normalized by dividing by the mean weight of each group. Third, standardized difference scores were used to assess whether balance of covariates was achieved between the comparison groups. Unlike P values, for which the magnitude is highly related to the sample size, standardized difference is a unified approach to quantifying the magnitude of difference between groups regardless of sample size; an absolute value less than 0.10 is considered a negligible difference (13, 14) Finally, separately weighte