The clinical utilization of intravenous immune globulin in patients with septic shock: a national census and retrospective cohort study
| dc.contributor.author | Leeies, Murdoch | |
| dc.contributor.examiningcommittee | Katz, Alan (Community Health Sciences) Kumar, Anand (Internal Medicine) | en_US |
| dc.contributor.supervisor | Zarychanski, Ryan (Community Health Sciences) | en_US |
| dc.date.accessioned | 2019-09-04T13:12:59Z | |
| dc.date.available | 2019-09-04T13:12:59Z | |
| dc.date.issued | 2019-08-19 | en_US |
| dc.date.submitted | 2019-08-19T18:15:24Z | en |
| dc.date.submitted | 2019-09-03T19:04:09Z | en |
| dc.degree.discipline | Community Health Sciences | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Background Sepsis is a systemic inflammatory response to infection. Septic shock is the result of a physiologic decompensation in patients with life-threatening infections. Septic shock ranks among the leading causes of death for critically ill patients worldwide. Despite advances in early identification and supportive treatment, the burden of sepsis remains high. The clinical investigation of therapeutic targets in sepsis has been notable for numerous negative trials and has not revealed effective interventions beyond antibiotics and supportive care. Intravenous immune globulin (IVIG) is a plasma product derived from human serum. It is administered routinely in autoimmune, inflammatory and immune deficiency states. Preliminary evidence supports beneficial effects of IVIG in sepsis but heterogeneity in study design and treatment effects, as well as changing standards of care over time, has limited uptake of IVIG in clinical practice. A rigorous evaluation of the efficacy, safety and cost-effectiveness of IVIG is required. The intravenous Immune Globulin in Sepsis (InVIGIS) research program will comprehensively evaluate the efficacy, safety and cost-effectiveness of IVIG in patients with septic shock. Hypothesis My overarching hypothesis is that IVIG will improve survival when used as an adjunctive therapy in the management of adult patients with septic shock. Objectives The aims of my thesis are (1) to establish respondent-reported practice patterns of IVIG in septic shock, (2) to identify facilitators and barriers to the use of IVIG in septic shock, (3) to better understand what has limited the uptake of previous research of IVIG in septic shock and the expected value of further information to inform best-practice, (4) to determine willingness to participate in a future clinical trial of IVIG in septic shock, (5) to describe clinical utilization patterns of IVIG in patients with septic shock, (6) to characterize the patient populations in which clinicians are prescribing IVIG for septic shock, (7) to identify determinants of IVIG use in patients with septic shock, (8) to evaluate the effectiveness of IVIG in patients with septic shock when added to usual care. Methods This multicomponent thesis includes a mixed-mode national census of Canadian academic critical care and infectious diseases physician specialists. The design and administration of this survey was conducted in accordance with evidenced-based survey science guidelines utilizing principles of social exchange theory. I also conducted a retrospective cohort study of adult patients with septic shock in a population representative database. I used descriptive methods to identify current utilization patterns of IVIG in clinical practice, multivariable conditional logistic regression modelling techniques to identify predictors of IVIG utilization as well as the clinical effectiveness of IVIG with respect to in-hospital mortality. Results In my survey of Canadian critical care medicine and infectious diseases physicians 91% (n = 333) of respondents reporting having ever prescribed IVIG as an adjunctive therapy in septic shock. The majority of respondents (91%) also felt that limitations in existing published evidence was the greatest barrier to the routine use of IVIG in septic shock. Respondents were overwhelmingly willing to participate in future research with 98% willing to consider enrolling their own patients in a future clinical trial. In a nationally-representative cohort IVIG was administered in 0.3% (685/268,502) of cases of septic shock across the United States. IVIG was positively associated with in-hospital mortality (OR 1.35 (95% CI 1.14-1.6) when controlling for available covariates in a multivariable regression analysis. Conclusions In a national survey of Canadian critical care medicine and infectious diseases physicians the majority of respondents reported experience using IVIG in patients with septic shock. They acknowledged, however, that insufficient evidence for efficacy was the greatest barrier to routine use of IVIG in patients with septic shock. Respondents overwhelmingly supported the need for further studies to clarify the role of IVIG in septic shock. In a retrospective analysis of a nationally-representative cohort the proportional utilization of IVIG in all cases of septic shock was low. IVIG was associated with decreased survival in a multivariable regression analysis. Variable dosing strategies, timing of therapy and residual confounding by indication were all possible influences on the association between IVIG and increased mortality. An adequately powered and designed prospective trial of IVIG in septic shock is required to determine the efficacy and safety of this therapy. | en_US |
| dc.description.note | October 2019 | en_US |
| dc.identifier.doi | https://doi.org/10.34991/VS2C-PP64 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/34142 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Septic Shock | en_US |
| dc.subject | Sepsis | en_US |
| dc.subject | IVIG | en_US |
| dc.subject | Intravenous Immune Globulin | en_US |
| dc.title | The clinical utilization of intravenous immune globulin in patients with septic shock: a national census and retrospective cohort study | en_US |
| dc.type | master thesis | en_US |