— General Surgery — Board Review Manual
Volume 10 Part 2
June 2011
Trauma of the Gastrointestinal Tract
Part 2 Available Online at no cost to you
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The Hospital Physician® General Surgery Board Review Manuals are published by Turner White Communications, Inc., an independent medical publisher dedicated to serving the information and education needs of clinical trainees and practicing physicians.
general surgery Board Review Manual Statement of Editorial Purpose The Hospital Physician General Surgery Board Review Manual is a study guide for residents and practicing physicians preparing for board examinations in general surgery. Each manual reviews a topic essential to current practice in the specialty of general surgery.
Trauma of the Gastrointestinal Tract Series Editor: Timothy A. Pritts, MD, PhD Associate Professor, Division of Trauma and Critical Care, Department of Surgery, University of Cincinnati, Cincinnati, OH
Contributors: Michael Petro, MD PUBLISHING STAFF PRESIDENT, Group PUBLISHER
Bruce M. White
Senior EDITOR
Robert Litchkofski
Assistant Professor of Surgery, Division of Trauma and Critical Care, Department of Surgery, University of Cincinnati, Cincinnati, OH
Gerald Fortuna, MD Clinical Instructor of Surgery, Division of Trauma and Critical Care, Department of Surgery, University of Cincinnati, Cincinnati, OH
Bryce RH Robinson, MD Assistant Professor, Division of Trauma and Critical Care, Department of Surgery, University of Cincinnati, Cincinnati, OH
executive vice president
Barbara T. White
executive director of operations
Jean M. Gaul
This work does not reflect the views of the United States Air Force or Department of Defense.
Table of Contents Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Esophageal Trauma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Injury to the Small Intestine. . . . . . . . . . . . . . . . . . . . . . . . 4
NOTE FROM THE PUBLISHER: This publication has been developed with out involvement of or review by the Amer ican Board of Surgery.
Trauma to the Colon and Rectum. . . . . . . . . . . . . . . . . . . 8 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
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www.hpboardreview.com General Surgery Volume 10, Part 2
General Surgery Board Review Manual
Trauma of the Gastrointestinal Tract Michael Petro, MD, Gerald Fortuna, MD, and Bryce RH Robinson, MD
INTRODUCTION The gastrointestinal (GI) tract runs from the mouth to the anus, passing through the head, neck, thorax, and abdomen. The GI tract is vulnerable to trauma in each of these areas. In blunt trauma, the small or large bowel may be injured in up to 5% to 10% of patients, with injury occurring secondary to direct compression, deceleration, or a rapid increase in intra-abdominal pressure.1 In penetrating trauma, all regions of the GI tract are vulnerable to missiles or blades. A thorough understanding of the evaluation and management of trauma to the GI tract is essential to surgeons who care for traumatically injured patients.
Esophageal Trauma Case Presentation 1 A 21-year-old man presents to the emergency department (ED) trauma resuscitation area 10 minutes after sustaining a gunshot wound to the neck. Upon arrival the patient is awake and alert with moderate anxiety. There is an obvious 5-mm wound at the midline just above the thyroid cartilage, with air exiting the wound on expiration. He is vocalizing with mild hoarseness and no dyspnea. Peripheral pulses are intact and symmetric. His heart rate is 104 bpm.
CASE 1 CONTINUED The physician notes that the patient is hemodynamically stable with a patent airway on arrival. Secondary survey demonstrates focal sensory and motor deficits of the right upper extremity. Cervical spine immobilization is continued with a hard collar. Plain films of the cervical spine and chest show a retained projectile and a likely cervical spine injury (Figure 1). There is no evidence of pneumothorax. Airway remains intact with no change in the subtle hoarseness of the patient’s voice. • Should this patient be intubated at this time? Although the patient has a patent airway at present, he has an obvious injury to the airway as evidenced by air exiting the wound. Blind intubation may inadvertently create a false passage in the submucosal space and thus worsen an injury or totally occlude the airway. Preferred options to secure this patient’s airway include fiberoptic image–guided intubation or placement of a surgical airway (tracheostomy) below the level of the injury. CASE 1 CONTINUED The patient undergoes an uneventful tracheostomy under local anesthetic and mild sedation in order to maintain his airway. Direct bronchoscopy performed at the time of his tracheostomy reveals an injury at the level of the vocal cords anteriorly. The patient remains hemodynamically stable without active bleeding from the wound or evidence of neck hematoma.
• What are the next steps in the assessment of this patient?
• Once the airway is secured, is formal neck exploration mandatory?
The first step is to assess the ABCs of trauma as described in the Advanced Trauma Life Support Course.1 The next step in management is to fully assess the patient for additional wounds or injuries and determine the location of projectiles. After removing all clothing, the patient must be promptly log rolled to look for additional wounds, and a chest radiograph should be obtained. Radiographs of the cervical spine may aid in assessing the location of the projectile. Given the risk for loss of airway, the patient can never be left unattended and should not be taken to the radiology department without a secured airway.
For the evaluation and care of trauma patients, the neck is often divided into 3 anatomical zones (Figure 2). By physical examination and imaging, the patient appears to have an injury in zone 2 of the neck. Traditional teaching in the care of trauma patients is that penetrating injuries to zones 1 and 3 are managed with a strategy of selective operative exploration and that hemodynamically stable patients undergo evaluation with endoscopy, esophagography, angiography, and bronchoscopy. In contrast, patients with injuries to zone 2 typically have undergone mandatory neck exploration
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Tr a u m a o f t h e G a s t r o i n t e s t i n a l Tr a c t
Figure 2. Zones of the neck as characterized for the care of the trauma patient. Zone 1 is from the clavicles to the cricoid cartilage. Zone 2 is from the cricoid to the angle of the mandible. Zone 3 is from the mandible to the base of the skull. (Adapted with permission from Borkon MJ, Cotton BA. Neck trauma. In: Brooks AJ, Clasper J, Midwinter M, et al., editors. Ryan’s ballistic trauma. 3rd ed. New York: Springer; 2011:397.)
Figure 1. Lateral cervical spine radiograph in patient 1 demonstrates likely cervical spine fracture as well as a retained projectile.
to evaluate for organ injury, an approach based in large part on data from a 1956 paper by Fogelman.2 This approach minimized missed injuries but resulted in a high rate of negative or nontherapeutic explorations.3,4 Since the 1980s, there has been a steady increase in the acceptance of selective surgical exploration for injuries in all zones of the neck. Indications for immediate operative exploration in patients sustaining penetrating trauma to the neck include hemodynamic instability and hard signs of vascular injury (arterial bleeding, expanding hematoma, bruit, airway compromise). The evaluation of patients who are hemodynamically stable and lack hard signs of vascular injury varies based on the presentation. Some authors advocate primary reliance on clinical exam,3,5,6 with angiography, esophagoscopy, or esophagram being utilized as needed based on physical exam or suspicion of injury. Other studies have advocated routine angiography and esophagography for all patients.7 There are several potential limitations to esophagography. The patient must be able to swallow and participate in the exam, and it may be challenging to evaluate oropharyngeal and hypopharyngeal injuries using this imaging study.8,9
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While this selective approach avoids unnecessary operation on many patients, it requires allocating significant resources to these patients and has been shown to increase overall morbidity. In addition to the direct risks of angiography and endoscopy, obtaining these studies can cause significant delays in operation.10 These delays have been linked to a doubling of esophageal-related complications.10,11 Based on these findings and the emergence of newer, faster computed tomography (CT) scanners, many centers now advocate the use of multislice helical CT angiography (MCTA) in the evaluation of penetrating neck trauma.12–14 MCTA of the neck for penetrating trauma often allows visualization of the trajectory of the projectile and evaluation of potential arterial injuries. If the images are of sufficient quality, they allow evaluation of soft tissue structures as well. By defining the trajectory of penetration, unnecessary endoscopy or esophagography may be avoided. In addition, the sensitivity of MCTA has been shown to be as high as traditional angiography for identifying surgically significant injuries in these patients.15 This allows a selective management approach that is minimally invasive and can be done in a timely manner. CASE 1 CONTINUED The patient is taken to the CT scanner where MCTA is performed. Imaging reveals the presence of significant air in the soft tissues of the neck as well as a projectile path through the posterior neck and
General Surgery Volume 10, Part 2
Tr a u m a o f t h e G a s t r o i n t e s t i n a l Tr a c t in near proximity to the esophagus. Based on these findings, the patient is taken to the operating room for rigid and flexible esophagoscopy. An 8-mm contusion without clear mucosal penetration is found at the level of the cricopharyngeus muscle. • What are the possible next steps in management? The endoscopic findings suggest that an esophageal injury is present. The next best steps are somewhat controversial. In this patient, the lack of a mucosal defect and the level of the contusion could allow nonoperative management of this injury. Extensive algorithms have been developed to allow nonoperative management in selected circumstances.16,17 Critical issues that must be considered include the kinetic energy associated with the wound (stab versus lowvelocity versus high-velocity gunshot wounds), level of the injury (hypopharynx versus cervical esophagus),18 and the timing until initial antibiotics. Most authors agree that any patient being observed for an esophageal penetrating injury must have, at most, a contained leak on contrast study. Some centers will limit this option to only those patients with no demonstrable leak on the swallow study. Injuries of the true cervical esophagus, below the constrictors, are less likely to heal with conservative management18 and thus are best managed operatively. Regardless of location, the most conservative option with penetrating neck trauma is to pursue operative exploration and repair. Penetrating thoracic and abdominal esophageal injuries are best managed with operation. • What are the operative approaches to the esophagus for trauma? In the neck, the cervical esophagus can be exposed via a collar incision if vascular injury is excluded, or an oblique incision along the anterior border of the sternocleidomastoid can be used if bilateral exposure is not needed. The left side is preferred unless the injury is a limited right-sided laceration. These incisions can be extended or combined as needed. Exposure of the esophagus will usually require division of the omohyoid. The carotid sheath is gently retracted laterally. Exposure is improved with division of the middle thyroid vein and inferior thyroid artery. Care must be taken to protect the recurrent laryngeal nerve. In the thoracic esophagus, the level of injury dictates the operative approach. The upper two-thirds are best approached by a right posterolateral thoracotomy. The lower third is best approached by a left-sided sixth or seventh rib posterolateral thoracotomy. In either case the exposure can be modified to an anterior thora-
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cotomy if the patient requires concurrent exposure to the abdominal cavity. On the right side, the azygos vein is divided and the lung retracted anteriorly. If the injury is very low in the chest, it may be best approached by laparotomy. Regardless of location, the full extent of the injury must be exposed and addressed while avoiding excessive mobilization of healthy tissue. In order to allow full evaluation of the extent of mucosal injury, the muscular layer should be opened proximally and distally to the injury prior to repairing the mucosa. Repair can be accomplished with a running absorbable monofilament suture in the mucosa and interrupted sutures in the muscularis. Care should be taken to avoid narrowing the esophageal lumen, and placement of an esophageal bougie at the time of repair may be helpful in this regard. In the cervical region, a flap of the strap muscles or sternocleidomastoid can be used to cover the repair. This is mandatory if there is a concomitant tracheal injury. In the chest, a flap can be created from the pleura or intercostal muscles in order to buttress the repair. In the distal esophagus, the gastric fundus can be used to buttress the repair or to patch a defect. Wide drainage of injuries is important, especially in the thoracic esophagus. It should be noted that in the narrow portion of the cervical esophagus, wide drainage without repair is an acceptable alternative to repair if that repair will cause narrowing of the lumen.18 In the rare case of tissue devastation or delayed diagnosis, the patient may require diversion with T-tube or fistula formation. CASE 1 CONCLUSION Because of the esophageal injury noted on endoscopy, the patient undergoes cervical exploration via a left sternocleidomastoid incision. At operation, a 2-cm laceration to the cervical esophagus is found. After local debridement of damaged tissue, this is repaired in 2 layers. Due to the presence of an airway injury, a local muscle flap is used to buttress the repair. A drain is placed. The patient recovers and is discharged to a rehabilitation facility on postoperative day 5.
INJURY TO THE SMALL INTESTINE CASE Presentation 2 A 21-year-old man is brought to the ED by ambulance after sustaining a single stab wound to the abdomen. He was reportedly hypotensive in the ambulance with a systolic blood pressure of 82 mm Hg. Emer-
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Tr a u m a o f t h e G a s t r o i n t e s t i n a l Tr a c t gency medical service (EMS) personnel began resuscitation with 2 L of crystalloid fluid through 2 large-bore peripheral intravenous (IV) lines with normalization of his blood pressure to the low 100s mm Hg systolic. He arrives in the resuscitation bay complaining of abdominal pain. He appears clammy and is cool to the touch. Initial vitals include a heart rate of 148 bpm and a systolic blood pressure of 92 mm Hg. His abdomen is mildly distended and slightly tender. Trauma labs are drawn and sent for point-of-care testing. • What clinical information can be determined from his initial response to resuscitation efforts? This patient’s tachycardia and initial hypotension are indicators that this injury may be more severe than appearances on physical exam alone would suggest. The patient has all the signs of significant hemorrhagic shock. The initial response to IV fluids, as has been taught in ATLS courses throughout the country, places this patient in a category described as a transient responder.1 The transient response to IV fluids, as noted by the EMS crew, suggests that this patient is suffering from ongoing hemorrhage. Together, the clinical findings and vital signs suggest that this patient is critically ill. • Should aggressive IV fluid resuscitation be started? A landmark study by Mattox in 1994 gave insight into the role of IV fluids in the pre-hospital care of patients with penetrating wounds to the torso.19 This study demonstrated that the timing of fluid resuscitation had a significant impact on patient outcomes, as patients randomized to aggressive early fluid resuscitation while en route to the hospital had a statistically significant increase in postoperative complications, longer hospital stays, and increased mortality.19 The finding that permissive hypotension may be beneficial to patients suffering from penetrating torso trauma has led to the practice of delaying initiation of aggressive IV fluid resuscitation until surgical control of bleeding is obtained in these patients, as long as the patient is mentating and has a palpable radial pulse. The strategy of permissive hypotension in trauma patients with penetrating torso injuries was further supported by a recent study which showed that patients randomized to a hypotensive resuscitation strategy received less crystalloid and fewer blood transfusions and developed less coagulopathy. In addition, they had a lower mortality rate in the early postoperative period.20 CASE 2 CONTINUED Primary and secondary surveys of the patient are rapidly completed. His airway is patent and
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breathing is intact. He has no obvious external hemorrhage. Upon removing his clothing, he is found to have a single 1-cm stab wound to the central portion of his abdomen. A focused assessment with sonography for trauma (FAST) exam is completed and reveals the presence of fluid in Morrison’s pouch and the pelvis. An upright chest radiograph shows no evidence of free air under the diaphragm. Lab tests show a hemoglobin of 9.8 g/dL, an INR of 1.6, a pH of 7.23, and a base deficit of –7. The massive transfusion protocol is activated. • What are the options for evaluating penetrating trauma to the abdomen? There are several options to evaluate the abdomen in patients suffering from penetrating trauma, including observation with serial abdominal examinations, FAST, diagnostic peritoneal lavage (DPL), CT imaging, direct exploration of the wound, diagnostic laparoscopy, and exploratory laparotomy. All of these options have a role in the management of penetrating trauma to the abdomen. The gold standard for penetrating injuries to the abdomen is exploratory laparotomy. However, because of nontherapeutic laparotomy rates as high as 23% to 53% in patients with stab wounds, selective nonoperative management algorithms have been developed.21 Exploratory laparotomy is mandated in hemodynamically unstable patients and those with peritonitis or evisceration. Patients not meeting these criteria may be considered for nonoperative management, as nontherapeutic laparotomies are associated with complication rates up to 41%.21 For these reasons, serial abdominal examinations, FAST, DPL, CT imaging, wound exploration, and laparoscopy have each found credible roles in the management of abdominal stab wounds. The use of serial abdominal examinations involves admission of the patient to the hospital and the performance of interval examinations, ideally by the same surgeon. The patient must be awake, alert, without a head injury, nonintoxicated, and able and willing to cooperate with examinations to be a candidate for this approach. If signs of intra-abdominal injury become evident, the patient is taken for exploration. Shaftan was the first surgeon to apply selective criteria to patients with traumatic injuries to the abdomen, finding no mortality in patients selected for observation. Operative intervention resulted in a significant number of nontherapeutic laparotomies.22 This selectively conservative approach to patients with abdominal stab wounds was later supported by several studies per-
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Tr a u m a o f t h e G a s t r o i n t e s t i n a l Tr a c t formed from 1960 to 1990 which found that a selective nonoperative approach to anterior abdominal wall stab wounds led to laparotomy being avoided in 52.8% to 88.6% of patients.21 FAST and DPL each are diagnostic techniques that allow evaluation of the patient for presence or absence of fluid in the peritoneum. FAST is best utilized to determine the presence or absence of hemoperitoneum in unstable patients, with the presence of hemoperitoneum leading to laparotomy.23 DPL has been utilized to evaluate for evidence of intraperitoneal injury, such as the presence of red blood cells, white blood cells, enteric contents, bile, or fecal matter.24 The use of CT scanning in the evaluation of penetrating stab wounds has been investigated extensively. Initial studies of patients who had been stabbed in the flank or back were able to show that nonoperative management could be successfully employed after a negative CT in 75.6% of the patients.21,25 A subsequent study reported that CT with oral and IV contrast had a sensitivity of 89%, a specificity of 98%, and an accuracy of 97% in the evaluation of stab wounds to the back.26 When IV, oral, and rectal contrast are used simultaneously, a negative CT scan study correlates with 100% sensitivity for retroperitoneal injuries in patients with back and flank stab wounds,21,27 making this approach the standard of care when evaluating this specific injury pattern. The use of helical CT in stab wounds to the anterior abdominal wall has also been investigated. The negative predictive value of helical CT in 1 early study was found to be 100%.21,28 In hemodynamically stable patients without clear signs for the need for emergency laparotomy, CT has become a clear beneficial adjunct in determining the clinical treatment plan. An additional technique used in evaluating abdominal stab wounds is direct exploration of the wound in the ED or the operating room. If penetration of the anterior fascial sheath of the abdominal wall is found, then many surgeons feel that exploratory laparotomy or diagnostic laparoscopy is indicated. Local wound exploration, if utilized, should be performed only by a surgeon skilled and experienced in evaluating traumatic injuries of the abdomen. Laparoscopy also plays a role in evaluating patients for possible intra-abdominal passage of a bullet or blade. The patient is taken to the operating room and a diagnostic laparoscope inserted. The surgeon evaluates for signs of peritoneal penetration, then performs a laparotomy as necessary. One very useful aspect of laparoscopy is in evaluating the diaphragm in patients who have thoracoabdominal wounds. In a prospective study
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by Yucel, 36 patients with left thoracoabdominal stab wounds were evaluated with laparoscopy.29 Of these patients, 13 (36.1%) were found to have injuries to the diaphragm and 7 of these 13 patients had associated intra-abdominal injuries. Of the patients with isolated diaphragm injuries, 9 were repaired laparoscopically. The use of each of these strategies for evaluating the abdomen in penetrating trauma depends on the clinical presentation of the patient at the time of assessment and the clinical judgment of the surgeon evaluating the patient. CASE 2 CONTINUED Due to the patient’s hemodynamic instability, he is taken emergently to the operating room for an exploratory laparotomy. In the operating room, he is found to have a significant amount of hemoperitoneum with enteric contents staining several loops of bowel. The abdomen is packed in a systematic fashion and the hemoperitoneum evacuated. There are multiple lacerations to the mesentery supplying the small bowel. These are controlled by surgical ligation of the actively bleeding vessels and then the mesenteric defects are oversewn, controlling the hemorrhage. • What is the blood supply to the small bowel? The arterial supply to the small bowel is predominantly from the superior mesenteric artery and its branches and arcades. The blood supply to the duodenal bulb comes directly from the hepatic artery, with a rich supply of collaterals from the gastroduodenal artery.30 The second and third portions of the duodenum are supplied by a complex arcade of vessels from the anterior and posterior superior pancreaticoduodenal arteries arising from the gastroduodenal artery, as well as the anterior and posterior inferior pancreaticoduodenal arteries from the superior mesenteric artery.30 It is important to note that the second and third portions of the duodenum share a common blood supply with the head of the pancreas, which often makes repairs to injuries suffered in this area more complicated. The fourth portion of the duodenum and the first portion of the jejunum just distal to the ligament of Treitz are supplied by the first jejunal branch of the superior mesenteric artery.30 The superior mesenteric artery supplies the jejunum and ileum through a series of branches that terminate in arcades in the mesentery of the small bowel. The intestinal arteries, or vasa recta, arise from the peripheral arcades near the mesenteric border of the small bowel, directly supplying the small bowel without anastomosing.30 The vasa recta bifurcate as they near the bowel wall. The length of the vasa recta
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Tr a u m a o f t h e G a s t r o i n t e s t i n a l Tr a c t Table 1. American Association for the Surgery of Trauma Grading Scale for Small Bowel Injury Grade*
Type of Injury
Description of Injury
I
Hematoma
Contusion or hematoma without devascularization
Laceration
Partial thickness, no perforation
II
Laceration
Laceration < 50% of circumference
III
Laceration
Laceration ≥ 50% of circumference without transection
IV
Laceration
Transection of the small bowel
V
Laceration
Transection of the small bowel with segmental tissue loss
Vascular
Devascularized segment
*Advance 1 grade for multiple injuries up to grade III. Adapted with permission from Moore EE, Cogbill TH, Malangoni MA, et al. Organ injury scaling, II: Pancreas, duodenum, small bowel, colon, and rectum. J Trauma 1990;30:1427-9.
can be used to distinguish the jejunum from the ileum, as jejunal vasa recta are long and straight, while in the ileum, the vasa recta are shorter and more tortuous.30 In general, the venous drainage of the bowel follows the arterial supply, draining into the superior mesenteric vein and then the portal vein. CASE 2 CONTINUED The intra-abdominal packs are removed and the solid organs are evaluated with no evidence of traumatic injury found. The intestines are then meticulously inspected from the diaphragmatic hiatus to the rectum. The lesser sac is opened and found to be normal. Special attention is paid to the mesenteric border at the vasa recta where the 2 leafs of the mesentery meet the bowel to identify any small perforations caused from the knife wound. Two large lacerations to the antimesenteric portion of the jejunum are found and contamination is controlled with rapid placement of interrupted sutures. On the proximal ileum, an additional injury is found that is very minor. The rest of the intra-abdominal contents appear normal as do all 3 zones of the retroperitoneum. During the operation, the surgeon discusses the patient’s resuscitation with the anesthesiologist. The surgeon is informed that the patient has received 12 units of packed red blood cells, 11 units of fresh frozen plasma, and a 10 pack of platelets. He is now hemodynamically stable with a pulse in the 90s and a systolic blood pressure of 117 mm Hg. • What options are there to finish the operation and repair the patient’s injuries? Whenever a patient presents with severe metabolic derangement, the use of damage control laparotomy strategies should be considered. In patients with
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severe ongoing acidosis and coagulopathy, rapid completion of the initial operation, packing of the abdomen, and performing bowel resection without anastomosis should be considered. At the second operation, bowel continuity can be restored, the abdomen thoroughly examined for missed injuries, and the abdomen then closed. Although useful and potentially lifesaving, this technique should be employed selectively. A recent study has suggested that delayed abdominal closure is associated with increased anastomotic leak rates.31 Options to repair small bowel injuries include repair or resection with anastomosis. The severity of small bowel injury is graded by the American Association for the Surgery of Trauma (AAST) small bowel injury scale (Table 1).32 In general, grade I hematomas may be amenable to observation. Grade I and II lacerations are typically repaired, with care taken not to narrow the intestinal lumen. One clinical study demonstrated equivalence between primary handsewn repair and resection with stapled anastomosis.33 Repair may be accomplished with either a single-layer or two-layer technique as dictated by the surgeon’s experience and preference. If the injury involves more than 50% of the bowel circumference (AAST grade III or above; Table 1) or if repair is not practical, resection and anastomosis will likely represent the best surgical option. The technique for anastomosis (stapled versus handsewn) remains an area of some controversy. One study showed no significant differences between these 2 techniques.33 A retrospective study from multiple level 1 trauma centers suggested that the handsewn technique may be superior to stapled, with increased intra-abdominal complication rates associated with stapled (13%) as compared to handsewn (5%) anastomosis.34 A more recent metaanalysis indicates that single-layer anastomosis is not in-
General Surgery Volume 10, Part 2
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Figure 3. Abdominal radiograph of patient 3. A retained projectile is noted in the right lower quadrant. An additional entrance wound is marked with a paperclip.
ferior to 2 layers.35 At present, the choice of anastomotic techniques is based on overall patient characteristics as well as time required to complete the repairs. Case 2 Conclusion Due to the excellent response to resuscitation, the avoidance of coagulopathy during the operation, and the lack of a large amount of enteric contamination within the peritoneal cavity, the surgeon performs a 2-layered primary repair of the small injury at the proximal ileum. The larger injury to the jejunum is resected with a stapling device and a stapled anastomosis performed. The abdomen is closed in a standard fashion with a running absorbable monofilament suture. The patient is transferred to the surgical intensive care unit postoperatively, where he recovers well. He is discharged home in good condition on postoperative day 6.
TRAUMA TO THE COLON AND RECTUM CASE Presentation 3 A 23-year-old man presents to the ED with multiple gunshot wounds to the abdomen. In transport, EMS began IV fluids through 2 large-bore
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lines and found 2 wounds to his anterior abdomen. On arrival, the primary survey performed by the trauma team demonstrates a tachycardic (heart rate 158 bpm) and hypotensive (systolic blood pressure 87 mm Hg) patient who is protecting his airway and answering questions appropriately. Trauma labs are sent and a type and cross rapidly acquired. Upon rolling the patient both directions and examining his perineum, a larger hole is seen in the right posterior flank. A digital rectal exam demonstrates gross blood. Due to the patient’s class IV hemorrhagic shock, resuscitation is begun immediately with blood and plasma. The chest radiograph is normal. An abdominal radiograph demonstrates a foreign body at the right pelvic brim (Figure 3). There is an additional entrance wound with no corresponding projectile (Figure 3). The secondary survey is negative for additional injuries and the patient is taken emergently to the operating room. Upon opening the abdomen, gross hemoperitoneum is encountered and an obvious destructive injury is seen on the anterior cecum. After packing the 4 quadrants of the abdomen and allowing anesthesia to commence resuscitation, small defects of the transverse colon and sigmoid colon are also appreciated. • How has the treatment of penetrating colon injuries historically evolved? The earliest reports for the surgical management of penetrating trauma to the colon are based on military experience during World War I.36,37 Primary repair of these wounds was favored due to the lower mortality rate being described. Postoperative sepsis was common, leading to a mortality rate of 30%.38 Treatment of colon injuries during World War II was based on the perception of an increase in mortality due to primary repair in the hands of many young and inexperienced military surgeons. The U.S. Surgeon General then mandated the routine use of colostomy for all colon injuries by 1943, with the British following in 1944.39,40 Surgical principles of World War II were translated back to the civilian population in that many injuries were treated with colostomy for the next 30 years. Nonetheless, surgeons began to recognize that civilian penetrating injuries are often low velocity with less destructive force than military injuries, allowing for primary repair as a viable surgical option.41–43 • Which injuries of the colon are amendable to primary repair? Like other penetrating injuries to the abdomen, the principles of control of bleeding and contamination apply. With colonic injuries, one must decide on the
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Tr a u m a o f t h e G a s t r o i n t e s t i n a l Tr a c t Table 2. American Association for the Surgery of Trauma Grading Scale for Colon Injury Grade*
Type of Injury
Description of Injury
I
Hematoma
Contusion or hematoma without devascularization
Laceration
Partial thickness, no perforation
II
Laceration
Laceration < 50% of circumference
III
Laceration
Laceration ≥ 50% of circumference without transection
IV
Laceration
Transection of the colon
V
Laceration
Transection of the colon with segmental tissue loss
Vascular
Devascularized segment
*Advance 1 grade for multiple injuries up to grade III. Adapted with permission from Moore EE, Cogbill TH, Malangoni MA, et al. Organ injury scaling, II: Pancreas, duodenum, small bowel, colon, and rectum. J Trauma 1990;30:1427-9.
destructive nature of the wound and the ongoing hemodynamic physiology of the patient. Nondestructive wounds of the colon are often limited to injuries that have a minimal need for debridement. These wounds are often defined as grade I, II, and III wounds on the AAST Colon Injury Scale (Table 2).32 Multiple authors have demonstrated a lower complication rate and intraabdominal abscess rate with the use of primary repair versus diverting colostomy in this setting.44–47 Destructive colon wounds require segmental resection secondary to a loss of significant wall integrity or mesenteric injury. These wounds are often Colon Injury Scale IV or V injuries. The decision for segmental resection and primary anastomosis often takes into consideration the ongoing physiology of the patient, the timing of repair, and quantification of intra-abdominal contamination. Evidence supports the finding that transient hypotension preoperatively or intraoperatively does not affect outcome but that a sustained period of hypotension significantly increases mortality.44,45,48 The duration of time from injury until repair as an independent predictor of postoperative complications is less well defined. Fecal diversion is recommended in nondestructive wounds with operative delays exceeding 12 hours and in destructive wounds with longer than 6 hours of delay with fecal peritonitis and hypotension.49 The degree to which fecal contamination from colonic injury impacts outcomes is unclear. It is difficult to objectively quantify the amount of such spillage. Nonetheless, when major contamination is defined as spillage in greater than 1 abdominal quadrant, its impact on increased intra-abdominal infection is seen.44,50 Prospective data for care of patients with destructive colon wounds is difficult to obtain because these wounds occur relatively rarely in civilian practice. The
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decision to repair as opposed to manage by diversion is multifactorial using criteria as described above. Demetriades and colleagues prospectively investigated this injury subtype to determine factors for mortality and septic morbidities in those undergoing resection and primary repair versus diversion.51 Univariate analysis demonstrated a difference for abdominal complications but not leak for those who received single-agent antibiotics, had severe fecal contamination, and received more than 4 units of packed blood cells. When multivariate analysis was performed, no difference was found for mortality or septic morbidities between the groups. The study group concluded that destructive colon injuries should be managed by resection and anastomosis rather than diversion, regardless of factors, due to the lack of evidence of benefit for a more conservative approach. Evidence-based guidelines for the management of penetrating colon injuries written prior to the above work take a more conservative approach.52 Pasquale and Fabian recommend resection and primary anastomosis in patients with destructive wounds (where > 50% of the bowel wall is injured or a devascularized segment is present) and in hemodynamically stable patients without evidence of shock, without significant underlying disease, with minimal associated injuries (injury severity score < 25), and without peritonitis.52 Of note, these guidelines are currently being rewritten. • Which type of anastomosis is preferred, sutured or stapled? If a colonic anastomosis is required, the preferable technique by which it is performed continues to be unclear. Brundage and colleagues demonstrated in 199 trauma patients at 5 trauma centers a significantly higher rate of anastomotic leak and intra-abdominal
General Surgery Volume 10, Part 2
Tr a u m a o f t h e G a s t r o i n t e s t i n a l Tr a c t abscess in those with stapled versus sutured gastrointestinal anastomoses.34 This work was contradicted by a large meta-analysis of randomized controlled trials that included 1233 patients with elective colorectal anastomoses and found no difference.53 Further work has demonstrated no superiority in technique for colonic anastomosis in traumatic, penetrating injuries and a decrease in leaks with the use of stapled ileocolic anastomoses in a large meta-analysis of elective interventions.54,55 At present, the decision to staple or sew gastrointestinal anastomoses is better left to the surgeon rather than predetermined by existing literature. CASE 3 CONTINUED After a period of aggressive resuscitation by anesthesia, an arterial source of hemorrhage is found in the ascending mesocolon. After ligation, the cecum and ascending colon are centrally mobilized, exposing a defect of the cecum that is more than 80% of the diameter. Posterior to the cecum, the tract of bullet can be reapproximated as it exited into the right flank, and a significant amount of fecal contamination is observed within the right lower quadrant. The patient has been hemodynamically stable since the initiation of resuscitation and no other vascular injuries are identified. A right hemicolectomy is performed with a stapled ileocolic anastomosis. Two small defects are seen on the anterior and posterior surface of the transverse colon, distal to the middle colic artery. The missile appears to be in the retroperitoneum and there is no major vascular injury or injury to adjacent structures. The transverse colon injuries are sutured closed in 2 layers. The small intestine is examined in its entirety and no injury is found. The lesser sac and stomach are free of injury. Upon inspection of the sigmoid colon, a single hole is seen on the anterior surface and a soft, nonexpanding hematoma is seen on the right lateral surface of the extraperitoneal rectum. A rigid proctoscopy is performed and no injury is seen; however, a significant amount of fresh blood compromises the exam.
pursue further testing.58 If a rectal injury is suspected, rigid proctoscopy should be performed. Proctoscopy for the diagnosis of rectal injuries has demonstrated sensitivity as high as 88% for extraperitoneal wounds. The sensitivity decreases dramatically with more proximal, intraperitoneal injuries.59 Screening for rectal injuries preoperatively may be impractical due to the patient’s condition. Intraoperative findings based on trajectory or extraperitoneal fullness or hematoma may suggest the presence of such an injury. Consideration should be given to intra-operative proctoscopy. Many trauma surgeons feel that extensive exploration of the extraperitoneal space in search of an injury is unwarranted in that visualization is difficult in a deep pelvis.60 In these cases, the presence of an injury should be presumed and the proper steps for treatment taken. • What are the 4 D’s of treating penetrating rectal injuries?
Isolated rectal injuries, though infrequent, are often caused by penetrating mechanisms, with gunshot wounds constituting the great majority.56,57 Like many uncommon wounds, a high index of suspicion needs to be maintained to avoid missing a potentially catastrophic injury. The evaluation of these injuries begins with digital rectal examination, but negative exams may not exclude a rectal injury. A finding of gross blood or a positive guaiac test should prompt the examiner to
Much like the treatment of penetrating colon injuries, the fundamentals for the treatment of rectal injuries are based on tenets proposed during the military conflicts of the last 70 years. The 4 D’s of rectal injury are: (1) debridement of nonviable tissue, (2) fecal diversion, (3) presacral drainage, and (4) distal washout. Although the techniques are utilized widely, whether to use them individually or in combination is controversial. The debridement of devitalized tissue along with primary repair and fecal diversion is often debated in the same manner in which destructive colon injuries are. Primary repair of rectal injuries is less controversial when they are located on the anterior or lateral surfaces of the upper two-thirds of the rectum that resides within the peritoneum. These wounds are analogous to colon wounds and should be treated as such. Wounds located in the extraperitoneal rectum, more specifically the lower one-third or posterior wall, may be repaired if visualization of the wound can occur easily without aggressive dissection.61 Civilian wounds that cannot be visualized easily are often diverted without other treatment in order to prevent abscess or contamination of pelvic soft tissue that could evolve into necrosis and pelvic sepsis.62 Fecal diversion is often employed in patients with destructive rectal injuries that would require complex repairs or in patients with ongoing hemodynamic instability. The use of presacral drainage in association with colostomy is often debated. A transperineal curved incision is made inferior to the anus to allow for blunt dissection in the retrorectal space up to the area of injury. Closed suction or Penrose drains are often employed, with removal
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• If a rectal injury is suspected, how should you proceed?
Tr a u m a o f t h e G a s t r o i n t e s t i n a l Tr a c t occurring when output is minimal. Such drainage is thought to prevent uncontrolled contamination and infection of the perirectal and retroperitoneal tissues. Such methods were utilized during the Korean War and Vietnam War with a resultant decrease in mortality.63 Similar beneficial outcomes have been found with civilian, lowvelocity injuries.57 However, Gonzalez et al demonstrated in a randomized, prospective study that mortality and morbidity did not increase when presacral drainage was omitted from fecal diversion.64 The use of irrigation into the distal rectum during operative intervention is also based upon improved mortality with its use during the Vietnam War.65 Surgeons utilized this technique to reduce the stool burden in the distal rectum to decrease pelvic soft tissue exposure to a large inoculum of bacteria. The use of this technique has been translated to a civilian population with debatable benefit. Many still advocate for this technique in patients with high-energy wounds.63 CASE 3 CONCLUSION The assumption that a rectal injury is present is made and the patient undergoes a diverting sigmoid colostomy and presacral drainage is employed with Penrose drains. The drains are removed after 3 days without incident. The patient is begun on a diet on postoperative day 3, and stool is noted in the colostomy bag by day 5, with hospital discharge by day 7. Six months later, a barium enema is performed without any findings of contrast extravasation or stricture of his rectal stump. His colostomy is closed at that time without complication.
REFERENCES 1. Advanced Trauma Life Support for Doctors. ATLS Student Course Manual. 8th ed. Chicago: American College of Surgeons Committee on Trauma; 2008. 2. Fogelman MJ, Stewart RD. Penetrating wounds of the neck. Am J Surg 1956;91:581–93. 3. Azuaje RE, Jacobson LE, Glover J, et al. Reliability of physical examination as a predictor of vascular injury after penetrating neck trauma. Am Surg 2003;69:804–7. 4. Noyes LD, McSwain NE Jr, Markowitz IP. Panendoscopy with arteriography versus mandatory exploration of penetrating wounds of the neck. Ann Surg 1986;204:21–31. 5. Demetriades D, Charalambides D, Lakhoo M. Physical examination and selective conservative management in patients with penetrating injuries of the neck. Br J Surg 1993;80:1534–6. 6. Demetriades D, Theodorou D, Cornwell E, et al. Evaluation of penetrating injuries of the neck: prospective study of 223 patients. World J Surg 1997;21:41–7. 7. Weigelt JA, Thal ER, Snyder WH 3rd, et al. Diagnosis of penetrating cervical esophageal injuries. Am J Surg 1987; 154:619–22.
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8. Ahmed N, Massier C, Tassie J, et al. Diagnosis of penetrating injuries of the pharynx and esophagus in the severely injured patient. J Trauma 2009;67:152–4. 9. Armstrong WB, Detar TR, Stanley RB. Diagnosis and management of external penetrating cervical esophageal injuries. Ann Otol Rhinol Laryngol 1994;103:863–71. 10. Asensio JA, Chahwan S, Forno W, et al.; American Association for the Surgery of Trauma. Penetrating esophageal injuries: multicenter study of the American Association for the Surgery of Trauma. J Trauma 2001;50:289–96. 11. Asensio JA, Berne J, Demetriades D, et al. Penetrating esophageal injuries: time interval of safety for preoperative evaluation--how long is safe? J Trauma 1997;43:319–24. 12. Inaba K, Munera F, McKenney M, et al. Prospective evaluation of screening multislice helical computed tomographic angiography in the initial evaluation of penetrating neck injuries. J Trauma 2006;61:144–9. 13. Osborn TM, Bell RB, Qaisi W, Long WB. Computed tomographic angiography as an aid to clinical decision making in the selective management of penetrating injuries to the neck: a reduction in the need for operative exploration. J Trauma 2008;64:1466–71. 14. Gracias VH, Reilly PM, Philpott J, et al. Computed tomography in the evaluation of penetrating neck trauma: a preliminary study. Arch Surg 2001;136:1231–5. 15. Munera F, Soto JA, Palacio D, et al. Diagnosis of arterial injuries caused by penetrating trauma to the neck: comparison of helical CT angiography and conventional angiography. Radiology 2000;216:356–62. 16. Madiba TE, Muckart DJ. Penetrating injuries to the cervical oesophagus: is routine exploration mandatory? Ann R Coll Surg Engl 2003;85:162–6. 17. Wu JT, Mattox KL, Wall MJ Jr. Esophageal perforations: new perspectives and treatment paradigms. J Trauma 2007;63:1173–84. 18. Stanley RB Jr, Armstrong WB, Fetterman BL, Shindo ML. Management of external penetrating injuries into the hypopharyngeal-cervical esophageal funnel. J Trauma 1997;42:675–9. 19. Bickell WH, Wall MJ Jr, Pepe PE, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 1994;331:1105–9. 20. Morrison CA, Carrick MM, Norman MA, et al. Hypotensive resuscitation strategy reduces transfusion requirements and severe postoperative coagulopathy in trauma patients with hemorrhagic shock: preliminary results of a randomized controlled trial. J Trauma 2011;70:652–63. 21. Como JJ, Bokhari F, Chiu WC, et al. Practice management guidelines for selective nonoperative management of penetrating abdominal trauma. J Trauma 2010;68:721–33. 22. Shaftan GW. Indications for operation in abdominal trauma. Am J Surg 1960;99:657–64. 23. Quinn AC, Sinert R. What is the utility of the Focused Assessment with Sonography in Trauma (FAST) exam in penetrating torso trauma? Injury 2011;42:482–7. 24. Rozycki GS, Root HD. The diagnosis of intraabdominal visceral injury. J Trauma 2010;68:1019–23. 25. Fletcher TB, Setiawan H, Harrell RS, Redman HC. Posterior abdominal stab wounds: role of CT evaluation. Radiology 1989;173:621–5. 26. Meyer DM, Thal ER, Weigelt JA, Redman HC. The role of abdominal CT in the evaluation of stab wounds to the back. J Trauma 1989;29:1226–8. 27. Himmelman RG, Martin M, Gilkey S, Barrett JA. Triple-contrast CT scans in penetrating back and flank trauma. J Trauma 1991;31:852–5.
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Tr a u m a o f t h e G a s t r o i n t e s t i n a l Tr a c t 28. Salim A, Sangthong B, Martin M, et al. Use of computed tomography in anterior abdominal stab wounds: results of a prospective study. Arch Surg 2006;141:745–50. 29. Yucel T, Gonullu D, Matur R, et al. Laparoscopic management of left thoracoabdominal stab wounds: a prospective study. Surg Laparosc Endosc Percutan Tech 2010;20:42–5. 30. Greenfield LJ, Mulholland MW. Greenfield’s surgery: scientific principles and practice. 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2011. 31. Burlew CC, Moore EE, Cuschieri J, et al. Sew it up! A Western Trauma Association multi-institutional study of enteric injury management in the postinjury open abdomen. J Trauma 2011;70:273–7. 32. Moore EE, Cogbill TH, Malangoni MA, et al. Organ injury scaling, II: Pancreas, duodenum, small bowel, colon, and rectum. J Trauma 1990;30:1427–9. 33. Witzke JD, Kraatz JJ, Morken JM, et al. Stapled versus hand sewn anastomoses in patients with small bowel injury: a changing perspective. J Trauma 2000;49:660–5. 34. Brundage SI, Jurkovich GJ, Hoyt DB, et al. Stapled versus sutured gastrointestinal anastomoses in the trauma patient: a multicenter trial. J Trauma 2001;51:1054–61. 35. Shikata S, Yamagishi H, Taji Y, et al. Single- versus two-layer intestinal anastomosis: a meta-analysis of randomized controlled trials. BMC Surg 2006;6:2. 36. Wallace C. A study of 1,200 cases of gunshot wounds of the abdomen. Br Med J 1916;4:679. 37. Fraser J, Drummond H. Three hundred perforating wounds of the abdomen. Br Med J 1917;1:321–30. 38. Fabian TC. Infection in penetrating abdominal trauma: risk factors and preventive antibiotics. Am Surg 2002;68:29–35. 39. Army Service Forces. Office of the Surgeon General. Circular Letter No. 178. October 23, 1943. 40. Ogilvie WH. Abdominal wounds in the Western Desert. Bull US Army Med Dep 1946;6:435–45. 41. Woodhall JP, Ochsner A. The management of perforating injuries of the colon and rectum in civilian practice. Surgery 1951;29:305–20. 42. Raj NB, Cheung SC, Rosztoczy I, Pitha PM. Mouse genotype affects inducible expression of cytokine genes. J Immunol 1992;148:1934– 40. 43. Stone HH, Fabian TC. Management of perforating colon trauma: randomization between primary closure and exteriorization. Ann Surg 1979;190:430–6. 44. George SM Jr, Fabian TC, Voeller GR, et al. Primary repair of colon wounds. A prospective trial in nonselected patients. Ann Surg 1989;209:728–33. 45. Demetriades D, Charalambides D, Pantanowitz D. Gunshot wounds of the colon: role of primary repair. Ann R Coll Surg Engl 1992;74:381–4. 46. Ivatury RR, Gaudino J, Nallathambi MN, et al. Definitive treatment of colon injuries: a prospective study. Am Surg 1993;59:43–9. 47. Gonzalez RP, Falimirski ME, Holevar MR. Further evaluation of
colostomy in penetrating colon injury. Am Surg 2000;66:342–6. 48. Baker LW, Thomson SR, Chadwick SJ. Colon wound management and prograde colonic lavage in large bowel trauma. Br J Surg 1990;77:872–6. 49. Maxwell RA, Fabian TC. Current management of colon trauma. World J Surg 2003;27:632–9. 50. Dang CV, Peter ET, Parks SN, Ellyson JH. Trauma of the colon: early drop-back of exteriorized repair. Arch Surg 1982;117:652–6. 51. Demetriades D, Murray JA, Chan L, et al; Committee on Multicenter Clinical Trials. American Association for the Surgery of Trauma. Penetrating colon injuries requiring resection: diversion or primary anastomosis? An AAST prospective multicenter study. J Trauma 2001;50:765–75. 52. Pasquale M, Fabian TC. Practice management guidelines for trauma from the Eastern Association for the Surgery of Trauma. J Trauma 1998;44:941–56. 53. Lustosa SA, Matos D, Atallah AN, Castro AA. Stapled versus handsewn methods for colorectal anastomosis surgery. Cochrane Database Syst Rev 2001;(3):CD003144. 54. Demetriades D, Murray JA, Chan LS, et al. Handsewn versus stapled anastomosis in penetrating colon injuries requiring resection: a multicenter study. J Trauma 2002;52:117–21. 55. Choy PY, Bissett IP, Docherty JG, et al. Stapled versus handsewn methods for ileocolic anastomoses. Cochrane Database Syst Rev 2007(3):CD004320. 56. Renz BM, Feliciano DV, Sherman R. Same admission colostomy closure (SACC). A new approach to rectal wounds: a prospective study. Ann Surg 1993;218:279–92. 57. Burch JM, Feliciano DV, Mattox KL. Colostomy and drainage for civilian rectal injuries: is that all? Ann Surg 1989;209:600–10 58. Levine H, Simon RJ, Smith TR, et al. Guaiac testing in the diagnosis of rectal trauma: what is its value? J Trauma 1992;32:210–2. 59. Hargraves MB, Magnotti LJ, Fischer PE, et al. Injury location dictates utility of digital rectal examination and rigid sigmoidoscopy in the evaluation of penetrating rectal trauma. Am Surg 2009;75:1069–72. 60. Duncan AO, Phillips TF, Scalea TM, et al. Management of transpelvic gunshot wounds. J Trauma 1989;29:1335–40. 61. Levine JH, Longo WE, Pruitt C, et al. Management of selected rectal injuries by primary repair. Am J Surg 1996;172:575–8. 62. Navsaria PH, Edu S, Nicol AJ. Civilian extraperitoneal rectal gunshot wounds: surgical management made simpler. World J Surg 2007;31:1345–51. 63. Shannon FL, Moore EE, Moore FA, McCroskey BL. Value of distal colon washout in civilian rectal trauma--reducing gut bacterial translocation. J Trauma 1988;28:989–94. 64. Gonzalez RP, Falimirski ME, Holevar MR. The role of presacral drainage in the management of penetrating rectal injuries. J Trauma 1998;45:656–61. 65. Lavenson GS, Cohen A. Management of rectal injuries. Am J Surg 1971;122:226–30.
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12 Hospital Physician Board Review Manual
TYG289752-01
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TYGACIL® (tigecycline) Brief Summary See package insert for full Prescribing Information. For further product information and current package insert, please visit www.wyeth.com or call our medical communications department toll-free at 1-800-934-5556. INDICATIONS AND USAGE TYGACIL is indicated for the treatment of adults with complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillinsusceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis. TYGACIL is indicated for the treatment of adults with complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros. TYGACIL is indicated for the treatment of adults with community-acquired pneumonia infections caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates), and Legionella pneumophila. CONTRAINDICATIONS TYGACIL is contraindicated for use in patients who have known hypersensitivity to tigecycline. WARNINGS AND PRECAUTIONS Anaphylaxis/Anaphylactoid Reactions Anaphylaxis/anaphylactoid reactions have been reported with nearly all antibacterial agents, including TYGACIL, and may be life-threatening. TYGACIL is structurally similar to tetracycline-class antibiotics and should be administered with caution in patients with known hypersensitivity to tetracycline-class antibiotics. Hepatic Effects Increases in total bilirubin concentration, prothrombin time and transaminases have been seen in patients treated with tigecycline. Isolated cases of significant hepatic dysfunction and hepatic failure have been reported in patients being treated with tigecycline. Some of these patients were receiving multiple concomitant medications. Patients who develop abnormal liver function tests during tigecycline therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing tigecycline therapy. Adverse events may occur after the drug has been discontinued. Mortality Imbalance and Lower Cure Rates in Ventilator-Associated Pneumonia A study of patients with hospital acquired pneumonia failed to demonstrate the efficacy of TYGACIL. In this study, patients were randomized to receive TYGACIL (100 mg initially, then 50 mg every 12 hours) or a comparator. In addition, patients were allowed to receive specified adjunctive therapies. The sub-group of patients with ventilator-associated pneumonia who received TYGACIL had lower cure rates (47.9% versus 70.1% for the clinically evaluable population) and greater mortality (25/131 [19.1%] versus 14/122 [11.5%]) than the comparator. Use During Pregnancy TYGACIL may cause fetal harm when administered to a pregnant woman. If the patient becomes pregnant while taking tigecycline, the patient should be apprised of the potential hazard to the fetus. Results of animal studies indicate that tigecycline crosses the placenta and is found in fetal tissues. Decreased fetal weights in rats and rabbits (with associated delays in ossification) and fetal loss in rabbits have been observed with tigecycline [see USE IN SPECIfIC POPULATIONS]. Tooth Development The use of TYGACIL during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). Results of studies in rats with TYGACIL have shown bone discoloration. TYGACIL should not be used during tooth development unless other drugs are not likely to be effective or are contraindicated. Clostridium difficile-Associated Diarrhea Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including TYGACIL, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. Patients With Intestinal Perforation Caution should be exercised when considering TYGACIL monotherapy in patients with complicated intra-abdominal infections (cIAI) secondary to clinically apparent intestinal perforation. In cIAI studies (n=1642), 6 patients treated with TYGACIL and 2 patients treated with imipenem/cilastatin presented with intestinal perforations and developed sepsis/ septic shock. The 6 patients treated with TYGACIL had higher APACHE II scores (median = 13) versus the 2 patients treated with imipenem/cilastatin (APACHE II scores = 4 and 6). Due to differences in baseline APACHE II scores between treatment groups and small overall numbers, the relationship of this outcome to treatment cannot be established. Tetracycline-Class Effects TYGACIL is structurally similar to tetracycline-class antibiotics and may have similar adverse effects. Such effects may include: photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia). As with tetracyclines, pancreatitis has been reported with the use of TYGACIL. Superinfection As with other antibacterial drugs, use of TYGACIL may result in overgrowth of non-susceptible organisms, including fungi. Patients should be carefully monitored during therapy. If superinfection occurs, appropriate measures should be taken. Development of Drug-Resistant Bacteria Prescribing TYGACIL in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, 2514 patients were treated with TYGACIL. TYGACIL was discontinued due to adverse reactions in 7% of patients compared to 6% for all comparators. Table 1 shows the incidence of treatment-emergent adverse reactions through test of cure reported in 2% of patients in these trials. Table 1. Incidence (%) of Adverse Reactions Through Test of Cure Reported in 2% of Patients Treated in Clinical Studies Body System TYGACIL Comparatorsa Adverse Reactions (N=2514) (N=2307) Body as a Whole Abdominal pain 6 4 Abscess 2 2 Asthenia 3 2 Headache 6 7 Infection 7 5 Cardiovascular System Phlebitis 3 4 Digestive System Diarrhea 12 11 Dyspepsia 2 2 Nausea 26 13 Vomiting 18 9 Hemic and Lymphatic System Anemia 5 6 Metabolic and Nutritional Alkaline Phosphatase Increased 3 3 Amylase Increased 3 2 Bilirubinemia 2 1 BUN Increased 3 1 Healing Abnormal 3 2 Hyponatremia 2 1 Hypoproteinemia 5 3 SGOT Increasedb 4 5 SGPT Increasedb 5 5 Respiratory System Pneumonia 2 2 Nervous System Dizziness 3 3 Skin and Appendages Rash 3 4
Vancomycin/Aztreonam, Imipenem/Cilastatin, Levofloxacin, Linezolid. LFT abnormalities in TYGACIL-treated patients were reported more frequently in the post therapy period than those in comparator-treated patients, which occurred more often on therapy. In all Phase 3 and 4 studies that included a comparator, death occurred in 4.0% (150/3788) of patients receiving TYGACIL and 3.0% (110/3646) of patients receiving comparator drugs. An increase in all-cause mortality has been observed across phase 3 and 4 clinical studies in TYGACIL treated patients versus comparator. The cause of this increase has not been established. This increase should be considered when selecting among treatment options. (See Table 2.) Table 2. Patients with Outcome of Death by Infection Type a
b
Infection Type cSSSI cIAI CAP HAP Non-VAPa VAPa RP DFI Overall Adjusted
n/N
TYGACIL
12/834 42/1382 12/424 66/467 41/336 25/131 11/128 7/553 150/3788
Comparator
%
n/N
1.4 3.0 2.8 14.1 12.2 19.1 8.6 1.3 4.0
6/813 31/1393 11/422 57/467 42/345 15/122 2/43 3/508 110/3646
%
Risk Difference* % (95% CI)
0.7 2.2 2.6 12.2 12.2 12.3 4.7 0.6 3.0
0.7 (-0.3, 1.7) 0.8 (-0.4, 2.0) 0.2 (-2.0, 2.4) 1.9 (-2.4, 6.3) 0.0 (-4.9, 4.9) 6.8 (-2.1, 15.7) 3.9 (-4.0, 11.9) 0.7 (-0.5, 1.8) 0.6 (0.1, 1.2)**
CAP = Community-acquired pneumonia; cIAI = Complicated intra-abdominal infections; cSSSI = Complicated skin and skin structure infections; HAP = Hospital-acquired pneumonia; VAP = Ventilator-associated pneumonia; RP = Resistant pathogens; DFI = Diabetic foot infections. * The difference between the percentage of patients who died in TYGACIL and comparator treatment groups. The 95% CI for each infection type was calculated using the normal approximation method without continuity correction. ** Overall adjusted (random effects model by trial weight) risk difference estimate and 95% CI. a These are subgroups of the HAP population. Note: The studies include 300, 305, 900 (cSSSI), 301, 306, 315, 316, 400 (cIAI), 308 and 313 (CAP), 311 (HAP), 307 [Resistant gram-positive pathogen study in patients with MRSA or Vancomycin-Resistant Enterococcus (VRE)], and 319 (DFI with and without osteomyelitis). In comparative clinical studies, infection-related serious adverse events were more frequently reported for subjects treated with TYGACIL (7%) versus comparators (6%). Serious adverse events of sepsis/septic shock were more frequently reported for subjects treated with TYGACIL (2%) versus comparators (1%). Due to baseline differences between treatment groups in this subset of patients, the relationship of this outcome to treatment cannot be established [see WARNINGS AND PRECAUTIONS]. The most common treatment-emergent adverse reactions were nausea and vomiting which generally occurred during the first 1 – 2 days of therapy. The majority of cases of nausea and vomiting associated with TYGACIL and comparators were either mild or moderate in severity. In patients treated with TYGACIL, nausea incidence was 26% (17% mild, 8% moderate, 1% severe) and vomiting incidence was 18% (11% mild, 6% moderate, 1% severe). In patients treated for complicated skin and skin structure infections (cSSSI), nausea incidence was 35% for TYGACIL and 9% for vancomycin/aztreonam; vomiting incidence was 20% for TYGACIL and 4% for vancomycin/aztreonam. In patients treated for complicated intra-abdominal infections (cIAI), nausea incidence was 25% for TYGACIL and 21% for imipenem/cilastatin; vomiting incidence was 20% for TYGACIL and 15% for imipenem/cilastatin. In patients treated for community-acquired bacterial pneumonia (CABP), nausea incidence was 24% for TYGACIL and 8% for levofloxacin; vomiting incidence was 16% for TYGACIL and 6% for levofloxacin. Discontinuation from tigecycline was most frequently associated with nausea (1%) and vomiting (1%). For comparators, discontinuation was most frequently associated with nausea (<1%). The following adverse reactions were reported infrequently (<2%) in patients receiving TYGACIL in clinical studies: Body as a Whole: injection site inflammation, injection site pain, injection site reaction, septic shock, allergic reaction, chills, injection site edema, injection site phlebitis Cardiovascular System: thrombophlebitis Digestive System: anorexia, jaundice, abnormal stools Metabolic/Nutritional System: increased creatinine, hypocalcemia, hypoglycemia Special Senses: taste perversion Hemic and Lymphatic System: partial thromboplastin time (aPTT), prolonged prothrombin time (PT), eosinophilia, increased international normalized ratio (INR), thrombocytopenia Skin and Appendages: pruritus Urogenital System: vaginal moniliasis, vaginitis, leukorrhea Post-Marketing Experience The following adverse reactions have been identified during postapproval use of TYGACIL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. Anaphylaxis/anaphylactoid reactions, acute pancreatitis, hepatic cholestasis, jaundice, and severe skin reactions, including Stevens-Johnson Syndrome. DRUG INTERACTIONS Warfarin Prothrombin time or other suitable anticoagulation test should be monitored if tigecycline is administered with warfarin [see CLINICAL PHARMACOLOGY (12.3) in full Prescribing Information]. Oral Contraceptives Concurrent use of antibacterial drugs with oral contraceptives may render oral contraceptives less effective. USE IN SPECIfIC POPULATIONS Pregnancy Teratogenic Effects—Pregnancy Category D [see WARNINGS AND PRECAUTIONS] Tigecycline was not teratogenic in the rat or rabbit. In preclinical safety studies, 14C-labeled tigecycline crossed the placenta and was found in fetal tissues, including fetal bony structures. The administration of tigecycline was associated with slight reductions in fetal weights and an increased incidence of minor skeletal anomalies (delays in bone ossification) at exposures of 5 times and 1 times the human daily dose based on AUC in rats and rabbits, respectively (28 mcg·hr/mL and 6 mcg·hr/mL at 12 and 4 mg/kg/day). An increased incidence of fetal loss was observed at maternotoxic doses in the rabbits with exposure equivalent to human dose. There are no adequate and well-controlled studies of tigecycline in pregnant women. TYGACIL should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers Results from animal studies using 14C-labeled tigecycline indicate that tigecycline is excreted readily via the milk of lactating rats. Consistent with the limited oral bioavailability of tigecycline, there is little or no systemic exposure to tigecycline in nursing pups as a result of exposure via maternal milk. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TYGACIL is administered to a nursing woman [see WARNINGS AND PRECAUTIONS]. Pediatric Use Safety and effectiveness in pediatric patients below the age of 18 years have not been established. Because of effects on tooth development, use in patients under 8 years of age is not recommended [see WARNINGS AND PRECAUTIONS]. Geriatric Use Of the total number of subjects who received TYGACIL in Phase 3 clinical studies (n=2514), 664 were 65 and over, while 288 were 75 and over. No unexpected overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity to adverse events of some older individuals cannot be ruled out. No significant difference in tigecycline exposure was observed between healthy elderly subjects and younger subjects following a single 100 mg dose of tigecycline [see CLINICAL PHARMACOLOGY (12.3) in full Prescribing Information]. Hepatic Impairment No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh A and Child Pugh B). In patients with severe hepatic impairment (Child Pugh C), the initial dose of tigecycline should be 100 mg followed by a reduced maintenance dose of 25 mg every 12 hours. Patients with severe hepatic impairment (Child Pugh C) should be treated with caution and monitored for treatment response [see CLINICAL PHARMACOLOGY (12.3) and DOSAGE AND ADMINISTRATION (2.2) in full Prescribing Information]. OVERDOSAGE No specific information is available on the treatment of overdosage with tigecycline. Intravenous administration of TYGACIL at a single dose of 300 mg over 60 minutes in healthy volunteers resulted in an increased incidence of nausea and vomiting. In single-dose intravenous toxicity studies conducted with tigecycline in mice, the estimated median lethal dose (LD50) was 124 mg/kg in males and 98 mg/kg in females. In rats, the estimated LD50 was 106 mg/kg for both sexes. Tigecycline is not removed in significant quantities by hemodialysis. This Brief Summary is based on TYGACIL direction circular LAB-0458-2.0, revised 01/11.
TYG279434 © 2011 Pfizer Inc. All rights reserved. Printed in USA/February 2011
TYGACIL is in the IDSA/SIS guidelines for cIAI and the SIS guidelines for cSSSI.1,2
Expanded broad-spectrum coverage* is on your side
*TYGACIL does not cover Pseudomonas aeruginosa.
TYGACIL is indicated for the treatment of adults with: s Complicated skin and skin structure infections CAUSED BY Escherichia coli, Enterococcus faecalis VANCOMYCIN SUSCEPTIBLE ISOLATES Staphylococcus aureus METHICILLIN SUSCEPTIBLE AND RESISTANT ISOLATES Streptococcus agalactiae Streptococcus anginosus GRP INCLUDES S. anginosus, S. intermedius AND S. constellatus Streptococcus pyogenes Enterobacter cloacae Klebsiella pneumoniae AND Bacteroides fragilis s Complicated intra-abdominal infections CAUSED BY Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Enterococcus faecalis VANCOMYCIN SUSCEPTIBLE ISOLATES Staphylococcus aureus METHICILLIN SUSCEPTIBLE AND RESISTANT ISOLATES Streptococcus anginosus GRP INCLUDES S. anginosus S. intermedius AND S. constellatus Bacteroides fragilis Bacteroides thetaiotaomicron Bacteroides uniformis Bacteroides vulgatus Clostridium perfringens AND Peptostreptococcus micros s Community-acquired bacterial pneumonia CAUSED BY Streptococcus pneumoniae PENICILLIN SUSCEPTIBLE ISOLATES INCLUDING CASES WITH CONCURRENT BACTEREMIA Haemophilus influenzae BETA LACTAMASE NEGATIVE ISOLATES AND Legionella pneumophila
Important Safety Information s 4 9'!#), IS CONTRAINDICATED IN PATIENTS WITH KNOWN HYPERSENSITIVITY TO TIGECYCLINE s !NAPHYLAXISANAPHYLACTOID REACTIONS HAVE BEEN REPORTED WITH NEARLY ALL ANTIBACTERIAL AGENTS INCLUDING TIGECYCLINE AND MAY BE LIFE THREATENING 49'!#), SHOULD BE ADMINISTERED WITH CAUTION IN PATIENTS WITH KNOWN HYPERSENSITIVITY TO TETRACYCLINE CLASS ANTIBIOTICS s )SOLATED CASES OF SIGNIl CANT HEPATIC DYSFUNCTION AND HEPATIC FAILURE HAVE BEEN REPORTED IN PATIENTS BEING TREATED WITH TIGECYCLINE 3OME OF THESE PATIENTS WERE RECEIVING MULTIPLE CONCOMITANT MEDICATIONS 0ATIENTS WHO DEVELOP ABNORMAL LIVER FUNCTION TESTS DURING TIGECYCLINE THERAPY SHOULD BE MONITORED FOR EVIDENCE OF WORSENING HEPATIC FUNCTION !DVERSE EVENTS MAY OCCUR AFTER THE DRUG HAS BEEN DISCONTINUED s 4HE SAFETY AND EFl CACY OF 49'!#), IN PATIENTS WITH HOSPITAL ACQUIRED PNEUMONIA HAVE NOT BEEN ESTABLISHED s An increase in all-cause mortality has been observed across phase 3 and 4 clinical studies in TYGACIL-treated patients versus comparator-treated patients. The cause of this increase has not been established. This increase in all-cause mortality should be considered when selecting among treatment options s TYGACIL may cause fetal harm when administered to a pregnant woman s The use of TYGACIL during tooth development may cause permanent discoloration of the teeth. 49'!#), SHOULD NOT BE USED DURING TOOTH DEVELOPMENT UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED s !CUTE PANCREATITIS INCLUDING FATAL CASES HAS OCCURRED IN ASSOCIATION WITH TIGECYCLINE TREATMENT #ONSIDERATION SHOULD BE GIVEN TO THE CESSATION OF THE TREATMENT WITH TIGECYCLINE IN CASES SUSPECTED OF HAVING DEVELOPED PANCREATITIS s Clostridium difficile ASSOCIATED DIARRHEA #$!$ HAS BEEN REPORTED WITH USE OF NEARLY ALL ANTIBACTERIAL AGENTS INCLUDING 49'!#), AND MAY RANGE IN SEVERITY FROM MILD DIARRHEA TO FATAL COLITIS s -ONOTHERAPY SHOULD BE USED WITH CAUTION IN PATIENTS WITH CLINICALLY APPARENT INTESTINAL PERFORATION s 4 9'!#), IS STRUCTURALLY SIMILAR TO TETRACYCLINE CLASS ANTIBIOTICS AND MAY HAVE SIMILAR ADVERSE EFFECTS 3UCH EFFECTS MAY INCLUDE PHOTOSENSITIVITY PSEUDOTUMOR CEREBRI AND ANTI ANABOLIC ACTION WHICH HAS LED TO INCREASED "5. AZOTEMIA ACIDOSIS AND HYPERPHOSPHATEMIA !S WITH TETRACYCLINES PANCREATITIS HAS BEEN REPORTED WITH THE USE OF 49'!#), s 4O REDUCE THE DEVELOPMENT OF DRUG RESISTANT BACTERIA AND MAINTAIN THE EFFECTIVENESS OF 49'!#), AND OTHER ANTIBACTERIAL DRUGS 49'!#), SHOULD BE USED ONLY TO TREAT INFECTIONS PROVEN OR STRONGLY SUSPECTED TO BE CAUSED BY SUSCEPTIBLE BACTERIA !S WITH OTHER ANTIBACTERIAL DRUGS USE OF 49'!#), MAY RESULT IN OVERGROWTH OF NON SUSCEPTIBLE ORGANISMS INCLUDING FUNGI s 4HE MOST COMMON ADVERSE REACTIONS INCIDENCE ARE NAUSEA VOMITING DIARRHEA INFECTION HEADACHE AND ABDOMINAL PAIN s 0ROTHROMBIN TIME OR OTHER SUITABLE ANTICOAGULANT TEST SHOULD BE MONITORED IF 49'!#), IS ADMINISTERED WITH WARFARIN s #ONCURRENT USE OF ANTIBACTERIAL DRUGS WITH ORAL CONTRACEPTIVES MAY RENDER ORAL CONTRACEPTIVES LESS EFFECTIVE s 4HE SAFETY AND EFFECTIVENESS OF 49'!#), IN PATIENTS BELOW AGE AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED Please see brief summary of Prescribing Information on adjacent page. References: 1. 3OLOMKIN *3 -AZUSKI *% "RADLEY *3 ET AL $IAGNOSIS AND MANAGEMENT OF COMPLICATED INTRA ABDOMINAL INFECTION IN ADULTS AND CHILDREN GUIDELINES BY THE 3URGICAL )NFECTION 3OCIETY AND THE )NFECTIOUS $ISEASES 3OCIETY OF !MERICA Clin Infect Dis 2. -AY !+ 3TAFFORD 2% "ULGER %- ET AL 3URGICAL )NFECTION 3OCIETY 'UIDELINES 4REATMENT OF COMPLICATED SKIN AND SOFT TISSUE INFECTIONS Surg Infect 3. 49'!#),® TIGECYCLINE 0RESCRIBING )NFORMATION 7YETH 0HARMACEUTICALS )NC 49' © 0l ZER )NC !LL RIGHTS RESERVED 0RINTED IN 53!!PRIL
