|Year : 2018 | Volume
| Issue : 2 | Page : 115-119
Early hydrocortisone for multiple trauma patients may lower the incidence of nosocomial pneumonia
Mohamed Megahed1, Tamer Habib1, Islam Ahmed2, Mostafa Hefnawy1
1 Department of Critical Care Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt
2 Department of Clinical Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
|Date of Submission||13-Jun-2017|
|Date of Acceptance||31-Jan-2018|
|Date of Web Publication||28-Jun-2018|
21111, Department of Critical Care Medicine, Faculty of Medicine, Alexandria
Source of Support: None, Conflict of Interest: None
Background Early post-traumatic pneumonia increases the duration of mechanical ventilation (MV), hospitalization, and risk of death. In this study, the efficacy of hydrocortisone therapy in the prevention of nosocomial pneumonia in multiple trauma patients has been assessed.
Patients and methods Six hundred patients who were admitted with multiple trauma were randomly assigned into two groups. The early hydrocortisone (EH) group consisted of 300 patients who received intravenous hydrocortisone 200 mg/day within 24 h from admission or trauma for 5 days and 100 mg, 50 mg on the following 2 days, respectively. The no early hydrocortisone group consisted of 300 patients who received placebo. All patients were followed up for the incidence of noscomial pneumonia. The days of ICU stay, MV, and mortality rates were calculated in both groups as secondary outcomes.
Results The incidence of nosocomial pneumonia in the EH group was significantly lower than the no early hydrocortisone group [120 (40%) vs. 240 (80%), P<0.0001].The EH group showed shorter durations of ICU stay (9.89 vs. 13.6 days, P=0.0027) and MV (7.98±2.31 vs. 10.98±3.98, P=0.0031), respectively.
Conclusion The use of early intravenous stress dose of hydrocortisone in patients with multiple trauma may be associated with lower incidence of nosocomial pneumonia but with no difference in mortality.
Keywords: critical, hospital, hydrocortisone, nosocomial pneumonia, trauma
|How to cite this article:|
Megahed M, Habib T, Ahmed I, Hefnawy M. Early hydrocortisone for multiple trauma patients may lower the incidence of nosocomial pneumonia. Res Opin Anesth Intensive Care 2018;5:115-9
|How to cite this URL:|
Megahed M, Habib T, Ahmed I, Hefnawy M. Early hydrocortisone for multiple trauma patients may lower the incidence of nosocomial pneumonia. Res Opin Anesth Intensive Care [serial online] 2018 [cited 2020 Jun 4];5:115-9. Available from: http://www.roaic.eg.net/text.asp?2018/5/2/115/235490
| Background|| |
Severe trauma is a main worldwide leading cause of death and illness. The incidence of post-traumatic pneumonia is about 40–60%, mainly in patients with traumatic brain injury (TBI) ,,,. Early posttraumatic pneumonia increases the duration of mechanical ventilation (MV), hospitalization, and risk of death . So, preventing post-traumatic pneumonia is a major clinical and economical issue. Multiple trauma is defined as two or more traumatic injuries and an injury severity score higher than 15. Severe TBI is defined as a Glasgow Coma Scale score (GCS) of less than or equal to 8 after initial care .
Nosocomial pneumonia includes hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). VAP occurs more than 48 h after endotracheal intubation but HAP refers to pneumonia acquired at least 48 h after hospital admission in nonventilated patients. Large volume aspiration and depressed consciousness after trauma are associated with increased risk of nosocomial pneumonia. Nosocomial pneumonia is defined by the following parameters: two or more serial chest radiographs with infiltrate, consolidation, cavitation, fever more than 38°C (100.4°F) with no other recognized cause, leukopenia (<4000 white blood cells/mm3) or leukocytosis (≥12 000 white blood cells/mm3), new-onset purulent sputum or change in the character of sputum or increased respiratory secretions or increased suctioning requirements, new-onset or worsening cough, dyspnea, or tachypnea, rales or bronchial breath sounds, worsening gas exchange (as oxygen desaturation), increased oxygen requirements, or increased ventilator demand ,,,.
Trauma-related corticosteroid insufficiency was correlated with systemic inflammatory response syndrome (SIRS). It has been suggested that hydrocortisone attenuates the overwhelming inflammatory response without immunosuppression, restoring an adequate immune response to infection. The term critical illness corticosteroid insufficiency has replaced older terms as relative adrenal insufficiency and functional hypoadrenalism . Adrenal insufficiency in critical illness is best diagnosed by random total cortisol of less than 10 μg/dl (a baseline cortisol level in the single digits in the setting of refractory shock is diagnostic) or by positive adrenocorticotrophic hormone (ACTH) stimulation test (the change in cortisol level after the administration of 250 μg of ACTH is <9 μg/dl) ,,.
Hydrocortisone is the main corticosteroid agent used in the treatment of a wide variety of diseases and conditions principally for glucocorticoid effects as an anti-inflammatory and immunosuppressant agent and for its effects on blood and lymphatic systems in the palliative treatment of various diseases . Experimental and clinical data suggest that corticosteroid use may decrease the occurrence and or severity of nosocomial pneumonia in patients treated in ICUs ,,. We postulated that treatment with stress-dose levels of hydrocortisone would diminish the prevalence of nosocomial pneumonia . The aim of this study was to assess the efficacy of hydrocortisone therapy in the prevention of nosocomial pneumonia in multiple trauma patients.
| Patients and methods|| |
After ethical approval for this clinical trial from the local committee of ethics in the Faculty of Medicine of Alexandria University and the Department of Critical Care, informed consent was taken from the next of kin. This prospective, controlled study was conducted on patients admitted to the Critical Care Department with multiple trauma for more than 1 year. Patients were enrolled if they had an age from 18 to 64 years of both sexes (except pregnant women). We included all intubated multiple trauma patients (having two or more traumatic injuries and injury severity score of >15 or severe TBI) or expected to be MV for more than 48 h. We excluded any patients with previous adrenal insufficiency or immunosuppression. Any patient on corticosteroids therapy during last 6 months was also excluded.
All enrolled patients (n=600) were subjected on admission to complete history taking, complete physical examination and laboratory investigations. During admission the following parameters were monitored: vital signs, GCS, injury severity score, serial arterial blood gases and withdrawal of a blood sample for basal cortisol level for all patients to diagnose corticosteroid insufficiency defined as random total cortisol of less than 10 μg/dl or positive ACTH stimulation test (the change in cortisol level after the administration of 250 μg of ACTH is <9 μg/dl). Patients were randomly assigned into two groups by scientific randomizer sheet. The early hydrocortisone group (EH) consisted of 300 patients who received intravenous hydrocortisone 200 mg/day within 24 h from admission or trauma for 5 days and 100 mg, 50 mg on the following 2 days, respectively. For patients with corticosteroid insufficiency after receiving the results of basal cortisol level, hydrocortisone was stopped if patients had adapted corticosteroid function after 1 week of treatment. The no early hydrocortisone group (NEH) consisted of 300 patients who received a syringe containing isotonic saline as placebo.
All patients were followed up for the incidence of nosocomial pneumonia by monitoring vital signs every 4 h, daily arterial blood gases, assessment of pulmonary secretions, lab investigations as complete blood count and C-reactive protein, Chest radiography if at least two signs for the diagnosis of pneumonia appeared, fever, leukocytosis or leukopenia and cultures from sputum or any collected pulmonary secretions. The days of ICU stay, MV and mortality rates were calculated in both groups as secondary outcomes.
Data were collected onto an electronic spreadsheet and statistical package (SPSS, version 24) was used for statistical analyses. The Kolmogorov–Smirnov test was used to verify the normality of distribution of variables. Descriptive statistics were reported as raw percentages or means and SDs. A Student’s t-test or Mann–Whitney test was used when appropriate to compare means for parametric or nonparametric data, respectively. A χ2-test or Fisher’s exact test was performed for comparison of categorical variables. P value less than 0.05 was considered statistically significant.
| Results|| |
Regarding the baseline characteristics of patients in the two groups, there were no any significant differences between them in age or sex (P=0.980, 0.777, respectively). The age of the EH group ranged from 18 to 64 years with a mean of 38.23±12.44, in the NEH group it ranged from 19 to 68 years with a mean of 40.80±12.38 years. As regards GCS on admission, it ranged from 4 to 15 with a mean of 8.77±3.38 in the EH group, and 4–14 with a mean of 8.20±2.73 in the NEH group. GCS of both groups showed no significant difference (P=0.239). As regards Injury Severity Score, it ranged from 14–34 in the EH group and 16–34 with no significant difference between the two groups (P=0.336) ([Table 1]).
As regards our main study outcome, nosocomial pneumonia, the number of patients who were diagnosed with nosocomial pneumonia during their ICU stay was 360 (60%) patients. The incidence of nosocomial pneumonia in the EH group was significantly lower than the NEH group [120 (40%) vs. 240 (80%), P<0.0001]. There was a statistically significant difference between the two groups in ICU stay (9.89 vs. 13.6 days, P=0.0027) but without a clinical significance as we did not calculate the total days of in-hospital stay. The mortality rate in the EH group was lower than the NEH group but without any significant difference [30 (10%) vs. 40 (13.4%), P=0.699]. The EH group showed lower duration on MV than the NEH group (7.98±2.31 vs. 10.98±3.98) days and it was statistically significant (P=0.0031) ([Table 2]). The culture finding of sputum culture and bronchoalveolar lavages are shown in [Table 3].
| Discussion|| |
VAP is the most common nosocomial infection among critical care patients. Several studies have discussed that trauma patients, especially those with traumatic brain injury, were at a higher risk for VAP due to lower consciousness, pharyngeal aspiration and prolonged supine position than other trauma patients. Prevention of posttraumatic nosocomial pneumonia is challenging .
By summation of all the collected data and gathering the criteria for diagnosis of nosocomial pneumonia in both groups during their ICU stay, it was found that incidence and frequency of nosocomial pneumonia was significantly greater in the NEH group than patients treated with hydrocortisone in the EH group. Most of the cases were VAP. Roquilly et al.  included 149 patients; 20 (35.7%) of 56 patients in the hydrocortisone group and 31 (54.4%) of 57 patients in the placebo group developed HAP by day 28 (P=0.01). In the study by Bulger and Cuschieri , 47 (64.4%) patients in the hydrocortisone group and 37 (48.7%) patients in the placebo group were free of pneumonia episode. So both studies concluded that the stress dose of hydrocortisone in polytrauma patients was effective in decreasing the incidence of both early and late VAP. Also, Chaari et al.  studied 175 trauma patients, VAP was diagnosed in 49 (28%) and 59 episodes of VAP were recorded.
The data about culture findings showed that the most predominant organism in both groups were Klebsiella and Acinetobacter spp. Results in the study by Popovic et al. , which was conducted over 108 traumatic patients, showed that the dominating Gram-negative organism was Pseudomonas spp. and the dominating Gram-positive organism was methicillin-resistant Staphylococcus aureus. Similarly, in the study by Ibrahim et al. , Pseudomonas spp. was the most common Gram-negative organism isolated from the bronchoalveolar lavage cultures, while S. aureus was the most common Gram-positive one. Chaari et al.  results showed that Acinetobacter baumannii and Pseudomonas aeruginosa were the most common identified as causative microorganisms.
Findings about the duration on MV were significantly lower in the group who administered early hydrocortisone. In agreement of this study as regards days of MV, Roquilly et al.  and Bulger and Cuschieri  results showed that the mean duration on MV of the hydrocortisone group were 12 and 16 days in the placebo group with 4 days free of MV difference between the two groups (P=0.001).
The results of this study as about the days of ICU stay showed a significant decrease in the group on hydrocortisone (EH group) (P=0.0027). But, Chaari et al.  did not find a significant difference of VAP incidence between steroids positive and steroids negative groups (respectively, 29.3 and 26.5%; P=0.676). Our results were similar to the results of Roquilly et al.  and in Bulger and Cuschieri  ICU stay was 18 days with a median of 15 days in the hydrocortisone group while it was 24 with a median of 16 days in the placebo group. Also Ibrahim et al.  showed similar results. But, the results of Chaari et al.  have shown that the mean length of stay in the ICU was not significantly different between steroids positive and steroids negative groups (respectively, 11±9.7 and 12.3±10.7 days; P=0.372).
Results about mortality in this study have shown that hydrocortisone was not associated with a lower mortality rate. The EH group showed a slightly lower mortality rate than the NEH group but it was not statistically significant. Although the sample size was relatively large, no difference in mortality was detected. It may be due to that we collected data about all-cause mortality and further studies may find a significance. The results of this study were similar to the results in Roquilly et al.  and Bulger and Cuschieri : 5.3% of patients in the placebo group and 8.2% of patients in the hydrocortisone group died (P=0.44). Also, the results of Chaari et al.  have shown no mortality difference in the ICU between steroids positive and steroids negative groups (respectively, 29.3 and 24.1%; P=0.434).
| Conclusion|| |
The use of early intravenous stress dose of hydrocortisone in patients with multiple trauma in the ICU may be associated with lower incidence of nosocomial pneumonia including HAP and VAP and it may decrease the duration on MV but with no difference in mortality. Further studies on a larger scale are recommended to clarify these findings and find a direct correlation between mortality rate and the early use of hydrocortisone in such patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997; 349:1498–1504.
Bronchard R, Albaladejo P, Brezac G, Geffroy A, Seince PF, Morris W et al.
Early onset pneumonia: risk factors and consequences in head trauma patients. Anesthesiology 2004; 100:234–239.
Leone M, Delliaux S, Bourgoin A, Albanese J, Garnier F, Boyadjiev I et al.
Risk factors for late-onset ventilator-associated pneumonia in trauma patients receiving selective digestive decontamination. Intensive Care Med 2005; 31:64–70.
Lepelletier D, Roquilly A, Demeure dit latte D, Mahe PJ, Loutrel O, Champin P et al.
Retrospective analysis of the risk factors and pathogens associated with early-onset ventilator-associated pneumonia in surgical-ICU head-trauma patients. J Neurosurg Anesthesiol 2010; 22:32–37.
Osborn TM, Tracy JK, Dunne JR, Pasquale M, Napolitano LM. Epidemiology of sepsis in patients with traumatic injury. Crit Care Med 2004; 32:2234–2240.
Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R et al.
Guidelines for the management of severe traumatic brain injury. IX. Cerebral perfusion thresholds. J Neurotrauma 2007; 24(Suppl 1):S59–S64.
Morrow LE, Kollef MH. Recognition and prevention of nosocomial pneumonia in the intensive care unit and infection control in mechanical ventilation. Crit Care Med 2010; 38(Suppl):S352–S362.
Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB et al.
Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63:e61–e111.
Hunter JD. Ventilator associated pneumonia. BMJ 2012; 344:e3325.
Muscedere J, Dodek P, Keenan S, Fowler R, Cook D, Heyland D. Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: prevention. J Crit Care 2008; 23:126–137.
Burchard K. A review of the adrenal cortex and severe inflammation: quest of the ‘eucorticoid’ state. J Trauma 2001; 51:800–814.
Cohan P, Wang C, McArthur DL, Cook SW, Dusick JR, Armin B et al.
Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 2005; 33:2358–2366.
Offner PJ, Moore EE, Ciesla D. The adrenal response after severe trauma. Am J Surg 2002; 184:649–653. discussion 53–54.
Rushing GD, Britt RC, Collins JN, Cole FJ, Weireter LJ, Britt LD. Adrenal insufficiency in hemorrhagic shock. Am Surg 2006; 72:552–554.
Kaufmann I, Briegel J, Schliephake F, Hoelzl A, Chouker A, Hummel T et al.
Stress doses of hydrocortisone in septic shock: beneficial effects on opsonization-dependent neutrophil functions. Intensive Care Med 2008; 34:344–349.
Keh D, Boehnke T, Weber-Cartens S, Schulz C, Ahlers O, Bercker S et al.
Immunologic and hemodynamic effects of ‘low-dose’ hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med 2003; 167:512–520.
Confalonieri M, Urbino R, Potena A, Piattella M, Parigi P, Puccio G et al.
Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med 2005; 171:242–248.
American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171:388–416.
Chaari A, El Habib M, Ghdhoun H, Ben Algia N, Chtara K, Ben Hamida C et al.
Does low-dose hydrocortisone therapy prevent ventilator-associated pneumonia in trauma patients? Am J Ther 2015; 22:22–28.
Roquilly A, Mahe PJ, Seguin P, Guitton C, Floch H, Tellier AC et al.
Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study. JAMA 2011; 305:1201–1209.
Bulger EM, Cuschieri J. Steroids after severe injury: many unanswered questions. JAMA 2011; 305:1242–1243.
Popovic NA, Arsenijevic LJ, Filimonovic J, Rankovic V, Bumbasirevic V, Karamarkovic A. The frequency of ventilator associated pneumonia in polytraumatized patients: A-675. Eur J Anaesthesiol 2004; 21:166.
Ibrahim EH, Ward S, Sherman G, Kollef MH. A comparative analysis of patients with early-onset vs late-onset nosocomial pneumonia in the ICU setting. Chest 2000; 117:1434–1442.
[Table 1], [Table 2], [Table 3]