Practice Management Guideline

Parameters for Prophylactic Antibiotics in Tube Thoracostomy for Traumatic Hemopneumothorax

Chairman: Fred A. Luchette, MD
Members: Phil Barie, MD, Michael Oswanski, MD, David A. Spain, MD

I. Recommendations (For isolated chest trauma)

A. Level 1

There are insufficient data to support a level I recommendation as a standard of care.

B. Level 2

There are sufficient Class I & II data to recommend prophylactic antibiotic usage in patients receiving tube thoracostomy following chest trauma. A first generation cephalosporin should be used for no longer than 24 hours.

C. Level 3

Available data support a reduction in the incidence of pneumonia in trauma patients receiving prophylactic antibiotics when a tube thoracostomy is placed. There is insufficient data to suggest prophylactic antibiotics reduce the incidence of empyema.

II. Statement of the problem

Chest injury is a common problem in patients sustaining either blunt or penetrating trauma. Thoracic wounds account for 20 to 25% of all trauma deaths (16,000) annually.¹ Only 10 to 15% of all chest wounds require formal thoracotomy, whereas the remaining 85% can be managed with a closed tube thoracostomy. A major morbidity associated with this therapeutic device is empyema. The role of "prophylactic" antibiotics in reducing the incidence of this complication is controversial.

The value of antibiotic prophylaxis for elective and urgent operations in surgical practice has been validated by many studies.^2,3 For trauma patients, the purpose and optimal duration of antibiotic usage are less clear because there is no opportunity to administer the agent before bacterial contamination. Traditional teaching has held that antibiotics administered in this setting are being used for early presumptive therapy and thus are not prophylactic. The goal of this preventive therapy is the same as that of classic prophylactic therapy: to reduce the incidence of infectious events following a therapeutic intervention based on reasonable assumptions about the microorganisms most often encountered.

The goal of prophylactic antibiotic utilization in trauma patients requiring tube thoracostomy is to reduce the incidence of empyema and its associated morbidity. A secondary goal may be a reduction of bacterial pneumonitis but the literature is variable in this regard. The primary benefit must be significant because of the risk of emergence of resistant organisms with excessive use of antimicrobials. A major variable which confounds analysis is the setting and conditions under which the tube is inserted i.e., emergency room, intensive care unit, operating room.⁴ The incidence of empyema may also be affected by thoracostomy tube insertion by non-surgeon physicians. These factors are not mentioned in extant studies evaluating the role of prophylactic antibiotics with tube thoracostomy. Two other very important variables which have not been addressed appropriately in the literature are the choice of antimicrobial agent and the duration of therapy. Ideally, antibiotics with narrow coverage focused at the most common organisms for a brief duration would help reduce the risk of resistance and overall hospital costs.

III. Process

Identification of references

The recommended guidelines for prophylactic (preventive) antibiotic usage for trauma patients requiring a chest tube are evidence-based. A MEDLINE search for the past 20 years was performed. The following subject words were used for the query: antibiotic prophylaxis, chest tubes, human, drainage, tube thoracostomy, infection, empyema, bacterial infection-prevention and control. This identified 44 references in English. The bibliographies of each article were searched for additional references not identified by the original MEDLINE query. Letters to the editor, case reports, and review articles were excluded from further evaluation. Eleven articles were identified for inclusion in the evidentiary review. Nine were prospective series and two were meta-analyses. The articles were reviewed by four trauma surgeons and two pharmacologists who collaborated to produce these guidelines.

Quality of the references

The references were classified by the methodology established by the Agency for Health Care Policy and Research (AHCPR) of the U.S. Department of Health and Human Services. Additional criteria and specifications taken from a tool described by Oxman et al.⁵ were used for Class I articles. Thus, the classifications were:

Class I: Prospective, Randomized, Double-Blinded Study

Class II: Prospective, Randomized, Non-Blinded Trial

Class III: Retrospective Series of Patients or Meta-analysis

In the evidentiary table section is a summary of the eleven articles reviewed for these recommendations.

IV. Scientific Foundation

1. Historical background
2. Intrapleural infection received considerable attention as a complication of penetrating chest trauma in World War II.⁶ This problem continued to plague wartime surgeons during the Vietnam conflict despite the availability of antibiotics.⁷ The incidence of empyema following chest wounds has varied according to whether the reports originated from civilian or battlefield experience. During the pre-antibiotic era from 1922 to 1935, the reported incidence from Emory University was 2%. At the same institution, when all patients received antibiotics the incidence of empyema from 1948 to 1958 was 3%. Two World War II studies, in which most patients received either penicillin or sulfonamides, reported an incidence of empyema varying from 5 to 9.7%.^8,9 During the Korean war, Valle noted that hemothoraces became infected in 26% of cases. Fortunately, 80% of the patients recovered with thoracentesis and antibiotics.¹⁰ In contrast, Kahn et al. and Smythe et al. reported a much lower incidence of 1.6 to 2.1% in civilian practice when patients were treated with needle aspirations and antibiotics.^11,12 During the Vietnam war, Virgilio observed empyemas in 1.6% of patients treated with penicillin and streptomycin plus tube thoracostomy.¹³ A similar incidence of 0.5 to 1.5% was reported at the Martin Luther King Hospital in Los Angeles in two separate reports without routine antibiotic usage.^14,15

   Post-traumatic empyema is a significant problem in both blunt and penetrating chest injuries. Potential etiologies include (1) iatrogenic infection of the pleural space as during chest tube placement (2) direct infection resulting from penetrating injuries of the thoracic cavity (3) secondary infection of the pleural cavity from associated intraabdominal organ injuries with diaphragmatic disruption (4) secondary infection of clotted hemothorax (5) hematogenous or lymphatic spread of subdiaphragmatic infection to the pleural space (6) parapneumonic empyema resulting from post-traumatic pneumonia, pulmonary contusion, or acute respiratory distress syndrome (ARDS).

   The organisms responsible for the infection vary according to the mechanism of contamination. When related to chest tube insertion, the empyema typically will culture gram-positive Staphylococcus aureus or Streptococcus species. Secondary contamination from pneumonic processes or other routes of spread often involve gram-negative or mixed pathogens.

   The development of empyema increases patient morbidity, mortality, hospital length of stay, and the cost of the cure. Efforts to reduce the incidence of this complication will impact on morbidity and perhaps mortality. One possible intervention use of "prophylactic" antibiotics in patients requiring tube thoracostomy for traumatic hemothorax or pneumothorax. However, this is a misnomer in trauma patients. By definition, prophylactic antibiotic regimens achieve a pre-inoculation serum and tissue drug concentration before bacterial contamination, an impossibility in a trauma patient. Thus, antibiotic administration in the immediate post injury period is more correctly considered presumptive therapy.

3. Risk Factors for complications with tube thoracostomy after chest injury.

1) Mechanism of Injury

Chest trauma occurs as a result of stab, gunshot or blunt wounds. Cant et al. described the utility of first-generation cephalosporins in victims of thoracic stab wounds requiring tube thoracostomies.¹⁶ This is the only paper which controls patient enrollment by the mechanism of injury. They defined empyema as a need for thoracotomy and showed a significant reduction in those individuals receiving prophylactic antibiotics compared to control (0% vs 9%). However, of the five placebo-treated cases diagnosed with empyema, one developed as a result of underlying pneumonia and the other was an infected, retained hemothorax. The diagnosis of pneumonia was made only by the presence of a positive sputum culture. There was a significantly lower incidence of positive cultures in the group receiving antibiotics (12% vs 34%), and a significantly greater hospital length of stay and cost in the placebo group.

Three other studies evaluated the role of antibiotics in individuals with penetrating chest wounds.^17-19 Only one was a double-blinded randomized prospective study,¹⁷ whereas the other two were randomized but not blinded.^18,19 The majority of the patients in these three studies had received stab wounds (n=276) and only 67 were injured by firearms. The double-blinded study concluded that antibiotics reduced the incidence of empyema.¹⁷ The two randomized open-label studies did not see any benefit with the use of antibiotics.^18,19 The other studies^20-24 did not control for mechanism of injury; however, the majority of the patients in these studies sustained penetrating thoracic injuries. In one study, the specific mechanism of injury for the study population cannot be determined.²³ Another report included patients with spontaneous pneunothorax²⁰ (25% of the study cohort), which is irrelevant to trauma. These Class I and II studies do not support prophylactic antibiotics reducing the incidence of empyema or pneumonia in patients sustaining penetrating thoracic wounds as a standard of care.

2) Antimicrobial Agents

Only two of the papers reviewed utilized a first-generation cephalosporin in their study design.^16,23 The remainder of the studies used various antibiotics delivered via different routes. None of the papers evaluated the pharmacokinetics of the antimicrobials in the trauma patient. Grover et al. utilized clindamycin in an inadequate dosage.¹⁷ Doxycycline,¹⁸ cefoxitin²² and ampicillin¹⁹ each have little Staphylococcus coverage and represent less-than-ideal antibiotic prophylaxis for empyema. Four studies used appropriate agents and dosing.^16,20,21,24 Brunner et al. utilized cefazolin, however in an excessive dose.²³

Duration of antibiotic therapy for "prophylaxis" is usually confined to 24 hours. Only one study in this review limited antimicrobial usage to 24 hours.⁶ All other reports continued the agent being studied until the chest tube was removed^17-19,23,24 or for an additional 12 to 48 hours after it was removed.^20-22 For those receiving prophylaxis until the tube was removed, the number of days of intubation ranged from 3-6.5 days with the average being 4.7 days. Cant et al. (24- hour duration) reported no empyema in individuals prophylaxed with cefazolin compared to a 5% incidence in the placebo group.¹⁴ This is the only report which utilized 24-hour antibiotic prophylaxis with a reduction in empyema rates for patients with stab wounds to the chest.

3) Pneumonia/Empyema

The Centers for Disease Control and Prevention has clearly defined criterion for the diagnosis of pneumonia and empyema. These include clinical signs of sepsis, as well as positive cultures for a pathogen. Only three of the papers in this review had conforming definitions of these infectious complications.^20,22,24 The remainder of the studies had various non-standard definitions of pneumonia and empyema. Brunner et al. described two patients who underwent thoracotomy for entrapped lung but were culture-negative, which does not necessarily rule out empyema.²³ Nichols et al. described four control patients with empyema, however only one required decortication and one also had a pneumonia associated with the empyema (suggesting a parapneumonic empyema unrelated to the chest tube).²⁴

Two studies described an empyema in one patient each with retained hemothorax and a persistent pneumothorax.^18,21 Grover et al. described six patients with empyema, although only four required formal thoracotomy.¹⁷ One of these four had a necrotizing pneumonia, suggesting a parapneumonic process. The lack of a standardized definition of empyema in the various studies raises the question of the true incidence of chest tube-associated empyema, which may be less than actually stated in the literature. It also raises a question of the real incidence of empyema in the control groups as well. Nonetheless, the overall empyema rate for the control-group patients included in this review is 6.3% (29/464) compared to 0.5% (2/464) in patients receiving preventive antibiotics. The majority of the control patients were subsequently treated unnecessarily.

Because of the small number of patients in individual series, two meta-analyses have been performed.^25,26 Each concluded that prophylactic antibiotics have made a significant impact on the incidence of empyema. Both of these analyses assume that the study populations were similar when no objective information was supplied to support this assumption. The authors reported that all six studies met clinical combinability criteria without describing the specific criteria. The various antibiotics used in the studies over the fifteen-year period raises a question of comparative treatment regimens similar enough to draw any valid conclusions. These concerns, coupled with the multiple concerns in the above discussions raises questions about the conclusions from the meta-analysis papers.

4) Cost

Cost is a major concern in the current health care market. Only Nichols et al. and Cant et al. did any cost analysis in their studies.^16,24 Nichols et al. claimed that prophylactic antibiotics resulted in a 0.9 day reduction in length of hospital stay. At the time of that study, the wholesale cost for 1 gm cefonicid was $26.10. The treated patients received an average of 5 doses of that agent. The daily hospital cost quoted was $688 in government-run institutions and $820 in private for-profit facilities. They concluded that there was a potential saving of between $488 and $607 per patient (excluding cost of drug administration). When indirect cost are included, the cost savings is negligible. Clearly there is inadequate data to support any recommendations on cost analysis for prophylactic antibiotics.

IV. Evidentiary Table

The following 11 articles are those utilized to formulate these guidelines for prophylactic usage in trauma patients with a tube thoracostomy. The data are listed in chronologic order by year of publication. Included are: 4 Class I articles, 5 Class II and 2 Class III meta-analyses. The following data was retrieved and reported from each article: 1) antibiotic utilized, 2) the number of patients in each study group, 3) duration of prophylaxis in days, 4) incidence of pneumonia and 5) incidence of empyema. Mechanism of injury was also determined but not shown in the table.

V. Future Studies

The paucity of literature evaluating the role of prophylactic antibiotics in trauma patients receiving a tube thoracostomy for the chest trauma requires further clinical evaluation. Well designed multi-institutional trials with double-blinded design need to be performed. The studies should control for the setting in which the tube is being inserted and also the training of the physician performing the procedure. The patient at greatest risk is in shock in the emergency room. The intensive care unit and operating room should allow adequate time for strict sterile technique and minimized risk of iatrogenic contamination during insertion. Future studies should also control for time from administration until time of insertion, duration of prophylaxis, and mechanism of injury.

References

Evidentiary Table