Abstract
Context: Osteopathic manipulative treatment (OMT) is a promising adjunctive treatment for older adults hospitalized for pneumonia.
Objective: To report subgroup analyses from the Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) relating to hospital length of stay (LOS), ventilator-dependent respiratory failure rate, and in-hospital mortality rate.
Design: Multicenter randomized controlled trial.
Setting: Seven community hospitals.
Participants: Three hundred eighty-seven patients aged 50 years or older who met specific criteria for pneumonia on hospital admission.
Interventions: Participants were randomly assigned to 1 of 3 groups that received an adjunctive OMT protocol (n=130), a light touch (LT) protocol (n=124), or conventional care only (CCO) (n=133).
Main Outcome Measures: Outcomes for subgroup analyses were LOS, ventilator-dependent respiratory failure rate, and in-hospital mortality rate. Subgroups were age (50-74 years or ≥75 years), Pneumonia Severity Index (PSI) class (I-II, III, IV, or V), and type of pneumonia (community-acquired or nursing–home acquired). Data were analyzed by intention-to-treat and per-protocol analyses using stratified Cox proportional hazards models and Cochran-Mantel-Haenszel tests for general association.
Results: By per-protocol analysis of the younger age subgroup, LOS was shorter for the OMT group (median, 2.9 days; n=43) than the LT (median, 3.7 days; n=45) and CCO (median, 4.0 days; n=65) groups (P=.006). By intention-to-treat analysis of the older age subgroup, in-hospital mortality rates were lower for the OMT (1 of 66 [2%]) and LT (2 of 68 [3%]) groups than the CCO group (9 of 67 [13%]) (P=.005). By per-protocol analysis of the PSI class IV subgroup, the OMT group had a shorter LOS than the CCO group (median, 3.8 days [n=40] vs 5.0 days [n=50]; P=.01) and a lower ventilator-dependent respiratory failure rate than the CCO group (0 of 40 [0%] vs 5 of 50 [10%]; P=.05). By intention-to-treat analysis, in-hospital mortality rates in the PSI class V subgroup were lower (P=.05) for the OMT group (1 of 22 [5%]) than the CCO group (6 of 19 [32%]) but not the LT group (2 of 15 [13%]).
Conclusion: Subgroup analyses suggested adjunctive OMT for pneumonia reduced LOS in adults aged 50 to 74 years and lowered in-hospital mortality rates in adults aged 75 years or older. Adjunctive OMT may also reduce LOS and in-hospital mortality rates in older adults with more severe pneumonia. Interestingly, LT also reduced in-hospital mortality rates in adults aged 75 years or older relative to CCO. (ClinicalTrials.gov number NCT00258661)
Pneumonia is a major infectious disease afflicting elderly patients. While antibiotic therapy is the mainstay of treatment, the emergence of resistant bacteria is worrisome
1-3 and provides an impetus to explore adjunctive treatments. There are a few promising adjunctive nonpharmacologic treatments for pneumonia. Early mobilization (getting the patient out of bed daily from the first day of hospitalization) modestly reduced hospital length of stay (LOS) in community-acquired pneumonia.
4,5 A 2014 review
6 of 26 articles found that early mobilization reduced LOS and medical complications in an intensive care unit. One hospital-based clinical trial found that blowing bubbles into a bottle containing 10 cm of water, 10 times per day, reduced LOS in community-acquired pneumonia.
7 However, reviews of incentive spirometry have shown no definite benefit for preventing pulmonary complications after upper abdominal surgery
8 or complications after coronary artery bypass graft.
9 A meta-analysis of rotational bed therapy found that it decreased the incidence of pneumonia in selected critically ill patients but had no effect on duration of mechanical ventilation, number of days in intensive care, or hospital mortality.
10 Studies of classic chest physiotherapy for pneumonia have generally failed to show benefit.
11,12
Osteopathic manipulative treatment (OMT) is another nonpharmacologic adjunctive treatment for patients with pneumonia. Preliminary randomized controlled clinical trials suggested that OMT in hospitalized older patients reduced LOS and duration of intravenous antibiotic therapy.
13,14 Two systematic reviews of manual therapies, from perspectives outside the osteopathic medical profession, concluded that OMT is a promising treatment for patients with pneumonia.
15,16 A distinctive aspect of OMT is that many techniques were developed in the pre–antibiotic era specifically for the management of pneumonia.
17,18 The Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) sought to assess the efficacy of OMT as an adjunctive treatment for pneumonia in hospitalized older patients.
19 A detailed description of the MOPSE protocol
18 and the primary study outcomes
19 have been previously published. For the primary MOPSE outcomes, no between-group differences in LOS were found when intention-to-treat (ITT) analysis was used (n=387). When per-protocol (PP) analysis was used (n=318), OMT showed a reduction of 1 day in LOS and 0.5 days in the closely related duration of intravenous antibiotic therapy compared with conventional care only (CCO).
19 Treatment end points of ventilator-dependent respiratory failure and in-hospital mortality rates were 8% and 6% lower, respectively, in the OMT group compared with the CCO group for the PP analysis.
The purpose of the current article is to report subgroup analyses from MOPSE relating to LOS, ventilator-dependent respiratory failure rate, and in-hospital mortality rate. Because the benefits of OMT may vary by age or severity of illness, subgroup analyses were conducted to provide insight into characteristics of patients who were more likely to benefit from OMT. Differences between MOPSE treatment groups—OMT, light-touch (LT), and CCO—were evaluated for subgroups of participants based on their age, Pneumonia Severity Index (PSI), and type of pneumonia. Our hypothesis was that participants in MOPSE will have differing outcomes for LOS, ventilator-dependent respiratory failure rate, and in-hospital mortality rate for different ages, severity of illness, and type of pneumonia.
A multicenter randomized controlled clinical trial (ClinicalTrials.gov number NCT00258661), MOPSE was conducted between 2004 and 2007 at 7 community hospitals and enrolled patients aged 50 years or older who met specific criteria for pneumonia on their admission to the hospital. Details of the MOPSE protocol
18 and methods
19 have been previously published. The key methodologic elements related to our subgroup analyses are summarized here.
After providing informed consent, participants were randomly assigned to 1 of 3 groups: OMT, LT (sham control), or CCO (standard care control). Those participants assigned to the OMT or LT groups received standardized treatment protocols twice daily
18 for the duration of their hospital stay in addition to conventional care. The OMT protocol techniques included thoracolumbar soft tissue, rib raising, doming of the diaphragm with myofascial release, cervical spine soft tissue, suboccipital decompression, thoracic inlet myofascial release, thoracic lymphatic pump, and pedal pump. The LT protocol applied light touch to the same body regions in the same sequence and duration as the OMT protocol. The duration of each treatment session was approximately 20 minutes. The outcomes used for these subgroup analyses were LOS (defined by the date and time given on the admission and discharge orders), ventilator-dependent respiratory failure rate, and in-hospital mortality rate.
Data were analyzed by ITT analysis of all participants and by PP analysis of participants who finished the study without missing any protocol treatments. Data were analyzed for subgroups based on age (50-74 years or 75 years or older), PSI class (I-II, III, IV, or V), and type of pneumonia (community-acquired or nursing home–acquired). All analyses were stratified on the 5 study sites. The distribution of the participants across the treatment groups within each subgroup was compared with the distribution of the total participants across treatment groups using χ2 goodness-of-fit tests. To test the hypotheses regarding treatment group differences in LOS (measured in days), we used stratified Cox proportional hazards models, stratifying by study site. The LOS for participants who died in the hospital, had ventilator-dependent respiratory failure, or withdrew from the study was censored. The only variables included in the Cox proportional hazards model were the interaction of the treatment group with the subgroup, the main effect for the treatment group, and the main effect for the subgroup. The proportional hazards assumption was met within each of the strata; residuals were not evaluated. The treatment groups were compared for each level of the subgroup variable, and all pairwise comparisons between treatment groups were performed when a significant difference was observed. Cochran-Mantel-Haenszel tests for general association, stratifying on study site, were used to compare treatment groups on ventilator-dependent respiratory failure and in-hospital mortality rates for each subgroup separately, and all pairwise comparisons between treatment groups were performed when a significant difference was observed. P values less than .05 were considered statistically significant. The statistical analyses were performed using SAS version 9.1 (SAS Institute, Inc).
By ITT analysis, there was no significant difference in LOS between the treatment groups for any of the PSI class subgroups (
P≥.06) (
Table 2;
Figures 3A,
3C,
3E, and
3G). By PP analysis, there was a significant difference between the treatment groups in LOS for the PSI class IV subgroup (
P=.01) (
Table 2;
Figure 3F); LOS was shorter for the OMT group than the CCO group, but neither was different from the LT group. There was no significant difference in LOS between the treatment groups for PSI class I-II (
P=.14), III (
P=.26), or V (
P=.40) subgroups (
Table 2;
Figures 3B,
3D, and
3H, respectively). When only those with community-acquired pneumonia were included in the analysis of LOS for the PSI class subgroups, the results were consistent with the results for all participants.
There were no significant differences by ITT analysis between the treatment groups in ventilator-dependent respiratory failure rate for any of the PSI class subgroups (
P≥.07) (
Table 3;
Figures 4A,
4C,
4E, and
4G). By ITT analysis comparing the treatment groups in in-hospital mortality rate, the treatment groups were significantly different for the PSI class V subgroup (
P=.05) (
Table 3;
Figure 4G); the rate was lower for the OMT group than the CCO group, but neither was different from the LT group. There was no significant difference between the treatment groups in in-hospital mortality rate for the other PSI class subgroups (
P≥.18) (
Table 3;
Figures 4A,
4C, and
4E). Results for the PP analysis were similar to the ITT analysis with one exception (
Table 3;
Figures 4B,
4D,
4F, and
4H). For the PSI class IV subgroup, there was a significant difference between the treatment groups in ventilator-dependent respiratory failure rate (
P=.05) (
Table 3;
Figure 4F); the rate was lower for the OMT group than the CCO group, but neither was different from the LT group.
When only those with community-acquired pneumonia were included in the ITT analysis, there was a significant difference between the treatment groups in ventilator-dependent respiratory failure rate for the PSI class IV subgroup (P=.05); the rate was lower for the OMT group (0 of 38 [0%]; 95% CI, 0%-9%) than the CCO group (5 of 37 [14%]; 95% CI, 5%-29%), but neither was different from the LT group (2 of 31 [6%]; 95% CI,1%-21%). There were no significant differences between the treatment groups in ventilator-dependent respiratory failure rate for the other PSI class subgroups (P≥.47) or for in-hospital mortality rate for any of the PSI class subgroups (P≥.29). For the PP analysis of those with community-acquired pneumonia, there was a significant difference between the treatment groups in ventilator-dependent respiratory failure rate for the PSI class IV subgroup (P=.05); the rate was lower for the OMT group (0 of 40 [0%]; 95% CI, 0%-9%) than the CCO group (5 of 50 [10%]; 95% CI, 3%-22%), but neither was different from the LT group (1 of 35 [3%]; 95% CI, 0%-15%). There were no significant differences between the treatment groups in ventilator-dependent respiratory failure rate for the other PSI class subgroups (P≥.47). There was a significant difference between the treatment groups in in-hospital mortality rate for the PSI class V subgroup (P=.05); the rate was lower for the OMT group (0 of 12 [0%]; 95% CI, 0%-26%) than the CCO group (6 of 17 [35%]; 95% CI, 14%-62%), but neither was different from the LT group (2 of 10 [20%]; 95% CI, 3%-56%). There were no significant differences between the treatment groups in in-hospital mortality rate for the other PSI class subgroups (P≥.06).