Impact of Intravenous Immunoglobulin on Survival in Necrotizing Fasciitis With Vasopressor-Dependent Shock: A Propensity Score-Matched Analysis From 130 US Hospitals

Abstract

Background: Shock frequently complicates necrotizing fasciitis (NF) caused by group A Streptococcus (GAS) or Staphylococcus aureus. Intravenous immunoglobulin (IVIG) is sometimes administered for presumptive toxic shock syndrome (TSS), but its frequency of use and efficacy are unclear.

Methods: Adult patients with NF and vasopressor-dependent shock undergoing surgical debridement from 2010 to 2014 were identified at 130 US hospitals. IVIG cases were propensity-matched and risk-adjusted. The primary outcome was in-hospital mortality and the secondary outcome was median length of stay (LOS).

Results: Of 4127 cases of debrided NF with shock at 121 centers, only 164 patients (4%) at 61 centers received IVIG. IVIG subjects were younger with lower comorbidity indices, but higher illness severity. Clindamycin and vasopressor intensity were higher among IVIG cases, as was coding for TSS and GAS. In-hospital mortality did not differ between matched IVIG and non-IVIG groups (crude mortality, 27.3% vs 23.6%; adjusted odds ratio, 1.00 [95% confidence interval, .55-1.83]; P = .99). Early IVIG (≤2 days) did not alter this effect (P = .99). Among patients coded for TSS, GAS, and/or S. aureus, IVIG use was still unusual (59/868 [6.8%]) and lacked benefit (P = .63). Median LOS was similar between IVIG and non-IVIG groups (26 [13-49] vs 26 [11-43]; P = .84). Positive predictive values for identifying true NF and debridement among IVIG cases using our algorithms were 97% and 89%, respectively, based on records review at 4 hospitals.

Conclusions: Adjunctive IVIG was administered infrequently in NF with shock and had no apparent impact on mortality or hospital LOS beyond that achieved with debridement and antibiotics.

Keywords: intravenous immunoglobulin; necrotizing fasciitis.; toxic shock.

Figure 1.

Flowchart for the selection of necrotizing fasciitis (NF) shock cases. Inpatients discharged between October 2010 and June 2014 from 130 US academic medical centers and affiliates in the Vizient Clinical Database/Resource Manager (CDB-RM) were selected based on International Classification of Diseases, Ninth Revision (ICD-9) coding for NF, adult status, any surgical debridement, debridement consistent with the appropriate surgical management of true NF, vasopressor use, and absence of non–toxic shock syndrome (TSS) indications for intravenous immunoglobulin (IVIG). Numbers in brackets indicate the number of centers.

Figure 2.

Variation in volume of necrotizing fasciitis (NF) shock cases, proportion of admissions classified as NF-shock, and distributions of intravenous immunoglobulin (IVIG) use and associated dispensing restrictions across the US academic medical centers and affiliates in the Vizient Clinical Database/Resource Manager. A, Centers with at least 1 NF-shock case between October 2010 and June 2014 are ranked in ascending order of total case volume. Non-IVIG and IVIG cases are shown in blue and red, respectively. B, NF-shock cases are dichotomized based on whether IVIG dispensing is restricted at the treating center. The dispensing policy for IVIG was classified as restricted if prior approval was required from infectious diseases or pharmacy. The positive y-axis depicts NF-shock case density (non IVIG cases shown in blue; IVIG cases shown in red) for each hospital, ordered by increasing proportion of IVIG use in NF-shock, which is represented by the negative y-axis (black). Test of IVIG proportion medians between restricted and unrestricted centers by the Wilcoxon rank-sum test with continuity correction yielded a P value of .015, suggesting that restriction significantly reduced IVIG use for this indication.

Figure 3.

Distribution of propensity scores. Propensity scores are calculated from a logistic regression relating intravenous immunoglobulin (IVIG) group status as a binary outcome to the matching variables as predictors for 4127 individuals. Table 1 lists all the matching variables as well as their levels and categories. From the model, a fitted probability (propensity score) for each subject was calculated for how likely they are to be in the IVIG group based on their covariate profile of matching variable values. These 4127 propensity scores are visualized on the logit-scale in the figure for 4 groups, from top to bottom: unmatched IVIG (n = 3), matched IVIG (n = 161), matched non-IVIG (n = 161), unmatched non-IVIG (n = 3966). The 161 matched non-IVIG subjects are selected from all non-IVIG propensity scores so that the matched IVIG partner has a similar propensity score and with perfect balance on the presence of toxic shock syndrome, group A Streptococcus and/or Staphylococcus aureus codes, clindamycin use, and the value of first day of IVIG dose/vital status in the analysis. Note how similar the 161 propensity scores for the matched IVIG (n = 161) and matched non-IVIG (n = 161) groups are as opposed to how dissimilar the distributions are for matched IVIG (n = 161) and unmatched non-IVIG (n = 3966). The matched pairs are then put in a logistic regression model relating dichotomous variable in-hospital mortality to the matching variables and IVIG status as predictors. The exponentiated coefficient of the IVIG covariate in this subsequent logistic regression gives the adjusted odds ratio of mortality.

Figure 4.

In-hospital mortality across all analyses of intravenous immunoglobulin (IVIG) use in necrotizing fasciitis (NF) shock. The figure reports the odds ratios (ORs) of in-hospital mortality and 95% confidence intervals in the unmatched and unadjusted analysis, matched and unadjusted analysis, and primary analysis of all propensity-matched pairs adjusted by logistic regression, as well as sensitivity analyses on (1) propensity-matched pairs treated with clindamycin; (2) propensity-matched pairs where first administration of IVIG occurred within 2 days of hospitalization; and (3) propensity-matched pairs with coding for toxic shock syndrome (TSS), group A Streptococcus (GAS), and/or Staphylococcus aureus (SA) infection. There was no statistically significant difference in the ORs for in-hospital mortality between IVIG and propensity-matched non-IVIG cases in the primary analysis (*) as well as all sensitivity (†) analyses.