- Email: [email protected]
Tension Pneumothorax Complicating Endoscopic Retrograde Cholangiopancreatography: Case Report and Systematic Literature Review
Case Report
Tension Pneumothorax Complicating Endoscopic Retrograde Cholangiopancreatography: Case Report and Systematic Literature Review Yousef I. Al-Ashaal,1 Ashraf F. Hefny,1 Farouk Safi,2 Fikri M. Abu-Zidan,2 1Department of Surgery, Al-Ain Hospital and 2Department of Surgery, Faculty of Medicine and Health Sciences UAE University, Al-Ain, United Arab Emirates.
Perforation of the duodenum, which is usually retroperitoneal, is a known complication of endoscopic retrograde cholangiopancreatography (ERCP). Association of the duodenal perforation with pneumothorax is rare and the development of tension pneumothorax is even rarer. We report a case of tension pneumothorax following an ERCP, which we successfully treated with chest tube insertion and laparotomy, and systematically review the other 10 cases reported in the literature. Four of these 10 cases had tension pneumothorax. All were to the right side of the chest. Patients were mainly female (7/10). The median (range) age was 70.5 (55–89) years. Four patients required surgery (40%) and one patient, who was not operated on, died (10%). Clinicians should be aware of this serious complication. Unexplained chest pain, dyspnoea, and oxygen desaturation with abdominal distension during ERCP must raise this possibility. Early clinical recognition and prompt management is essential to improve the outcome. [Asian J Surg 2011;34(1):46–49] Key Words: endoscopic retrograde cholangiopancreatography, tension pneumothorax
Introduction
Case report
Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive procedure. It is usually indicated in the management of biliary and pancreatic diseases for stone extraction, prosthesis placement, and sphincterotomy.1 Perforation of the duodenum, which is usually retroperitoneal, is a known complication of ERCP.2,3 The association of the perforation with pneumothorax is rare and the development of tension pneumothorax is even rarer.4 Herein we report a case of tension pneumothorax following ERCP, and systematically review the literature on this topic.
A 25-year-old female was referred to our hospital from a private hospital with the diagnosis of acute calcular cholecystitis associated with common bile duct obstruction. She had epigastric pain radiating to the back of 3 days duration with associated dark urine. Abdominal examination has revealed a soft abdomen, tenderness at the epigastrium, and a positive Murphy’s sign. Total serum bilirubin was 27.4 μmol/L (normal < 17.1 μmol/L), alkaline phosphatase was 4.07 μkat/L (normal < 2.51 μkat/L), and C-reactive protein was 317 nmol/L (normal < 57 nmol/L). Serum amylase, blood glucose, serum electrolytes, and
Address correspondence and reprint requests to Professor Fikri Abu-Zidan, Department of Surgery, Faculty of Medicine and Health Sciences, PO Box 17666, Al-Ain, United Arab Emirates. E-mail: [email protected] ● Received: Dec 4, 2010 ● Revised: Dec 8, 2010 ● Accepted: Dec 8, 2010 © 2011 Elsevier. All rights reserved.
46
ASIAN JOURNAL OF SURGERY VOL 34 • NO 1 • JANUARY 2011
■ TENSION PNEUMOTHORAX COMPLICATING ERCP ■
white blood cell count were all normal. An abdominal ultrasound scan showed a distended gall bladder with a thickened wall and multiple calculi. The patient underwent ERCP. During the procedure, which was difficult, the patient suddenly developed abdominal distension, dyspnoea, decreased oxygen saturation, and diminished breath sounds on the right side of the chest. The procedure was abandoned and the patient was resuscitated and taken directly for a chest and abdominal computed tomography scan. This showed pneumoperitoneum, pneumoretroperitoneum (Figure 1), pneumomediastinum, and right side tension pneumothorax (Figure 2). The patient was initially managed conservatively with insertion of a right sided chest tube, nasogastric suction, and broad-spectrum antibiotics. Within 2 hours, the patient developed low grade
fever, and the abdomen became more distended and tender. We decided to conduct a laparotomy through a bilateral subcostal incision. A 2-cm perforation in the posteromedial aspect of the second part of the duodenum was identified. This was associated with mild laceration of the head of the pancreas with bile staining of the adjacent tissue (Figure 3). The perforation was repaired by a single layer of interrupted vicryl 3/0. Cholecystectomy with insertion of T tube into the common bile duct was performed and a naso-jejunal tube was fixed. Two drains were inserted at the pancreatic bed and subhepatic region. The postoperative period was uneventful. A gastrographin follow through study on day 9 and T-tube cholangiogram on day 10 were normal. The patient was discharged home on day 14. At 3 months postoperative follow-up, the patient was asymptomatic.
Discussion
Figure 1. Abdominal computed tomography scan showing intraperitoneal air (black arrow) and retroperitoneal air surrounding the kidneys (arrowheads).
Figure 2. Chest computed tomography scan showing tension pneumothorax of the right side pushing the heart to the left side.
ASIAN JOURNAL OF SURGERY VOL 34 • NO 1 • JANUARY 2011
ERCP is a routine procedure in the diagnosis and treatment of biliary and pancreatic diseases. In our hospital, an average of 70 ERCPs are performed every year. Common complications are pancreatitis, cholangitis, and perforation.3 ERCP can be difficult in the presence of a short intramural distal common bile duct, transampullary extraction of large gallstones, and repeated attempts of sphincterotomy. This would increase the risk of iatrogenic perforation.5 An ERCP-related perforation is usually retroperitoneal. Intraperitoneal perforation during ERCP may occur in a recently healed perforated duodenal ulcer.2,6 Duodenal perforation can cause pneumothorax and, very rarely, tension
Figure 3. Intraoperative picture showing a 2-cm perforation in the posteromedial aspect of the second part of the duodenum (arrow) associated with mild laceration of the head of the pancreas.
47
■ AL-ASHAAL et al ■
pneumothorax. To the best of our knowledge, 10 cases of pneumothorax (4 of them were tension pneumothorax) have been reported in the literature (Table 11–10). The age of our patient (25 years) was much younger than that of other reported patients where the median age (range) was 70.5 (55–89) years. The majority of reported patients were females (7/10). Duodenal perforation may be related to the thinning of the duodenal wall in this age group.7 Perforation occurs in about 2% of ERCP procedures and is usually diagnosed at the time of the procedure by observing contrast leakage.8 If the diagnosis is delayed, the mortality rate will be high.4,9 Most of the reported patients with duodenal perforation and pneumothorax (7 patients) had a difficult ERCP. The sudden development of unexplained chest pain, dyspnoea, oxygen desaturation, and abdominal distension should raise the suspicion of development of a pneumothorax.6 The diagnosis of pneumothorax can be confirmed by diminished
breath sounds, examination for hyper resonance, and use of fluoroscopy or a chest X-ray.4 We think that the diagnosis of pneumothorax in our patient was delayed and should have been detected and managed clinically before the computed tomography scan was performed. The amount of air leakage may not be related to the size of perforation but to the time of manipulation after the perforation.7 Once perforation has occurred, air can travel through the retroperitoneal plane into the thorax.6 Some authors postulate that the air will accumulate in the mediastinum and then rupture the mediastinal pleura to develop a pneumothorax. The torn pleura can act as a oneway valve causing tension pneumothorax.4 All reported patients who developed tension pneumothorax had it on the right side. In some patients, no duodenal perforation was found at laparotomy. Leakage of the air through the intestinal wall without a real perforation or as a result of a very minute duodenal perforation was suggested.5,8,11
Table 1. Summary of reported cases in the literature having pneumothorax as a complication of endoscopic retrograde cholangiopancreatography (ERCP)1–10 Reference no.
Age (yr)
Sex
Gya et al (1989)
8
63
Savides et al (1993)
7
Scarlett et al (1994) Morley et al (1997)
Author
Indications for ERCP
Type of pneumothorax
Female
Common bile duct stone
79
Female
9
59
2
Management
Outcome
Right
Chest tube insertion, laparotomy
Survived
Malignant obstructive jaundice
Bilateral
Bilateral chest tube insertion, laparotomy
Survived
Female
Common bile duct stone, postcholecystectomy
Right
Chest tube insertion
Survived
80
Female
Biliary stricture
Right tension
Chest tube insertion, laparotomy
Survived
10
89
Female
Acute cholecystitis
Right tension
Chest tube insertion
Survived
Lagoudianakis et al (2006)
1
55
Male
Gall bladder stones with jaundice
Right
Conservative only
Survived
Markogiannakis et al (2007)
5
56
Female
Acute cholecystitis, biliary obstruction
Bilateral
Bilateral chest tube insertion
Survived
Han et al (2008)
6
63
Male
Gall bladder stones with jaundice
Right tension
Chest tube insertion, laparotomy
Survived
Song et al (2009)
4
78
Female
Acute cholecystitis, biliary obstruction
Right tension
Chest tube insertion
Died
Ferrara et al (2009)
3
82
Male
Acute cholecystitis, biliary obstruction
Left
Chest tube insertion
Survived
25
Female
Acute cholecystitis, biliary obstruction
Right tension
Chest tube insertion, laparotomy
Survived
Hui et al (2001)
Present case (2010)
48
ASIAN JOURNAL OF SURGERY VOL 34 • NO 1 • JANUARY 2011
■ TENSION PNEUMOTHORAX COMPLICATING ERCP ■
The treatment of patients with suspected perforation of the duodenum associated with pneumothorax following ERCP remains controversial. The presence of a pneumothorax after ERCP is not a clear indication for surgical intervention.1 Most of the patients (6 patients) could be treated conservatively by chest drainage, nasogastric tube suction, and broad spectrum antibiotics.10 In patients with a deteriorating clinical picture or having continuous duodenal leakage confirmed by contrast studies, immediate laparotomy is essential. The delay in the diagnosis or operative intervention for such patients has a high morbidity and mortality.4,9 In contrast, in the five patients who had tension pneumothorax in Table 1, three (60%) needed laparotomy, and one, who refused surgery, died. In summary, tension pneumothorax with duodenal perforation is a rare complication of ERCP. It occurs mainly in the right side of the chest. The clinician should be aware of this serious complication. Unexplained chest pain, dyspnoea, and oxygen desaturation with abdominal distension during ERCP must raise this possibility. Early clinical recognition and prompt management is essential to improve the outcome.
References 1. Lagoudianakis EE, Tsekouras D, Papadima A, et al. Pneumothorax complicating endoscopic sphincterotomy successfully treated conservatively. Acta Gastroenterol Belg 2006;69:342–4.
ASIAN JOURNAL OF SURGERY VOL 34 • NO 1 • JANUARY 2011
2. Morley AP, Lau JY, Young RJ. Tension pneumothorax complicating a perforation of a duodenal ulcer during ERCP with endoscopic sphincterotomy. Endoscopy 1997;29:332. 3. Ferrara F, Luigiano C, Billi P, et al. Pneumothorax, pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and subcutaneous emphysema after ERCP. Gastrointest Endosc 2009; 69:1398–401. 4. Song SY, Lee KS, Na KJ, et al. Tension pneumothorax after endoscopic retrograde pancreatocholangiogram. J Korean Med Sci 2009;24:173–5. 5. Markogiannakis H, Toutouzas KG, Pararas NV, et al. Bilateral pneumothorax following endoscopic retrograde cholangiopancreatography: a case report. Endoscopy 2007;39(Suppl 1):E195. 6. Han ML, Wu YM, Liu KL, et al. Tension pneumothorax after an ERCP in a patient with hepatic hydrothorax and sealed-off perforated duodenal ulcer. Gastrointest Endosc 2008;68:771–2. 7. Savides T, Sherman S, Kadell B, et al. Bilateral pneumothoraces and subcutaneous emphysema after endoscopic sphincterotomy. Gastrointest Endosc 1993;39:814–7. 8. Gya D, Sali A, Angus D. Subcutaneous emphysema and pneumothorax following endoscopic sphincterotomy. Aust N Z J Surg 1989;59:900–2. 9. Scarlett PY, Falk GL. The management of perforation of the duodenum following endoscopic sphincterotomy: a proposal for selective therapy. Aust N Z J Surg 1994;64:843–6. 10. Hui CK, Lai KC, Yuen MF, et al. Tension pneumothorax complicating ERCP in a patient with a Billroth II gastrectomy. Gastrointest Endosc 2001;54:254–6. 11. Mosler P, Fogel EL. Massive subcutaneous emphysema after attempted endoscopic retrograde cholangiopancreatography in a patient with a history of bariatric gastric bypass surgery. Endoscopy 2007;39(Suppl 1):E155.
49
Tension Pneumothorax Complicating Endoscopic Retrograde Cholangiopancreatography: Case Report and Systematic Literature Review Yousef I. Al-Ashaal,1 Ashraf F. Hefny,1 Farouk Safi,2 Fikri M. Abu-Zidan,2 1Department of Surgery, Al-Ain Hospital and 2Department of Surgery, Faculty of Medicine and Health Sciences UAE University, Al-Ain, United Arab Emirates.
Perforation of the duodenum, which is usually retroperitoneal, is a known complication of endoscopic retrograde cholangiopancreatography (ERCP). Association of the duodenal perforation with pneumothorax is rare and the development of tension pneumothorax is even rarer. We report a case of tension pneumothorax following an ERCP, which we successfully treated with chest tube insertion and laparotomy, and systematically review the other 10 cases reported in the literature. Four of these 10 cases had tension pneumothorax. All were to the right side of the chest. Patients were mainly female (7/10). The median (range) age was 70.5 (55–89) years. Four patients required surgery (40%) and one patient, who was not operated on, died (10%). Clinicians should be aware of this serious complication. Unexplained chest pain, dyspnoea, and oxygen desaturation with abdominal distension during ERCP must raise this possibility. Early clinical recognition and prompt management is essential to improve the outcome. [Asian J Surg 2011;34(1):46–49] Key Words: endoscopic retrograde cholangiopancreatography, tension pneumothorax
Introduction
Case report
Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive procedure. It is usually indicated in the management of biliary and pancreatic diseases for stone extraction, prosthesis placement, and sphincterotomy.1 Perforation of the duodenum, which is usually retroperitoneal, is a known complication of ERCP.2,3 The association of the perforation with pneumothorax is rare and the development of tension pneumothorax is even rarer.4 Herein we report a case of tension pneumothorax following ERCP, and systematically review the literature on this topic.
A 25-year-old female was referred to our hospital from a private hospital with the diagnosis of acute calcular cholecystitis associated with common bile duct obstruction. She had epigastric pain radiating to the back of 3 days duration with associated dark urine. Abdominal examination has revealed a soft abdomen, tenderness at the epigastrium, and a positive Murphy’s sign. Total serum bilirubin was 27.4 μmol/L (normal < 17.1 μmol/L), alkaline phosphatase was 4.07 μkat/L (normal < 2.51 μkat/L), and C-reactive protein was 317 nmol/L (normal < 57 nmol/L). Serum amylase, blood glucose, serum electrolytes, and
Address correspondence and reprint requests to Professor Fikri Abu-Zidan, Department of Surgery, Faculty of Medicine and Health Sciences, PO Box 17666, Al-Ain, United Arab Emirates. E-mail: [email protected] ● Received: Dec 4, 2010 ● Revised: Dec 8, 2010 ● Accepted: Dec 8, 2010 © 2011 Elsevier. All rights reserved.
46
ASIAN JOURNAL OF SURGERY VOL 34 • NO 1 • JANUARY 2011
■ TENSION PNEUMOTHORAX COMPLICATING ERCP ■
white blood cell count were all normal. An abdominal ultrasound scan showed a distended gall bladder with a thickened wall and multiple calculi. The patient underwent ERCP. During the procedure, which was difficult, the patient suddenly developed abdominal distension, dyspnoea, decreased oxygen saturation, and diminished breath sounds on the right side of the chest. The procedure was abandoned and the patient was resuscitated and taken directly for a chest and abdominal computed tomography scan. This showed pneumoperitoneum, pneumoretroperitoneum (Figure 1), pneumomediastinum, and right side tension pneumothorax (Figure 2). The patient was initially managed conservatively with insertion of a right sided chest tube, nasogastric suction, and broad-spectrum antibiotics. Within 2 hours, the patient developed low grade
fever, and the abdomen became more distended and tender. We decided to conduct a laparotomy through a bilateral subcostal incision. A 2-cm perforation in the posteromedial aspect of the second part of the duodenum was identified. This was associated with mild laceration of the head of the pancreas with bile staining of the adjacent tissue (Figure 3). The perforation was repaired by a single layer of interrupted vicryl 3/0. Cholecystectomy with insertion of T tube into the common bile duct was performed and a naso-jejunal tube was fixed. Two drains were inserted at the pancreatic bed and subhepatic region. The postoperative period was uneventful. A gastrographin follow through study on day 9 and T-tube cholangiogram on day 10 were normal. The patient was discharged home on day 14. At 3 months postoperative follow-up, the patient was asymptomatic.
Discussion
Figure 1. Abdominal computed tomography scan showing intraperitoneal air (black arrow) and retroperitoneal air surrounding the kidneys (arrowheads).
Figure 2. Chest computed tomography scan showing tension pneumothorax of the right side pushing the heart to the left side.
ASIAN JOURNAL OF SURGERY VOL 34 • NO 1 • JANUARY 2011
ERCP is a routine procedure in the diagnosis and treatment of biliary and pancreatic diseases. In our hospital, an average of 70 ERCPs are performed every year. Common complications are pancreatitis, cholangitis, and perforation.3 ERCP can be difficult in the presence of a short intramural distal common bile duct, transampullary extraction of large gallstones, and repeated attempts of sphincterotomy. This would increase the risk of iatrogenic perforation.5 An ERCP-related perforation is usually retroperitoneal. Intraperitoneal perforation during ERCP may occur in a recently healed perforated duodenal ulcer.2,6 Duodenal perforation can cause pneumothorax and, very rarely, tension
Figure 3. Intraoperative picture showing a 2-cm perforation in the posteromedial aspect of the second part of the duodenum (arrow) associated with mild laceration of the head of the pancreas.
47
■ AL-ASHAAL et al ■
pneumothorax. To the best of our knowledge, 10 cases of pneumothorax (4 of them were tension pneumothorax) have been reported in the literature (Table 11–10). The age of our patient (25 years) was much younger than that of other reported patients where the median age (range) was 70.5 (55–89) years. The majority of reported patients were females (7/10). Duodenal perforation may be related to the thinning of the duodenal wall in this age group.7 Perforation occurs in about 2% of ERCP procedures and is usually diagnosed at the time of the procedure by observing contrast leakage.8 If the diagnosis is delayed, the mortality rate will be high.4,9 Most of the reported patients with duodenal perforation and pneumothorax (7 patients) had a difficult ERCP. The sudden development of unexplained chest pain, dyspnoea, oxygen desaturation, and abdominal distension should raise the suspicion of development of a pneumothorax.6 The diagnosis of pneumothorax can be confirmed by diminished
breath sounds, examination for hyper resonance, and use of fluoroscopy or a chest X-ray.4 We think that the diagnosis of pneumothorax in our patient was delayed and should have been detected and managed clinically before the computed tomography scan was performed. The amount of air leakage may not be related to the size of perforation but to the time of manipulation after the perforation.7 Once perforation has occurred, air can travel through the retroperitoneal plane into the thorax.6 Some authors postulate that the air will accumulate in the mediastinum and then rupture the mediastinal pleura to develop a pneumothorax. The torn pleura can act as a oneway valve causing tension pneumothorax.4 All reported patients who developed tension pneumothorax had it on the right side. In some patients, no duodenal perforation was found at laparotomy. Leakage of the air through the intestinal wall without a real perforation or as a result of a very minute duodenal perforation was suggested.5,8,11
Table 1. Summary of reported cases in the literature having pneumothorax as a complication of endoscopic retrograde cholangiopancreatography (ERCP)1–10 Reference no.
Age (yr)
Sex
Gya et al (1989)
8
63
Savides et al (1993)
7
Scarlett et al (1994) Morley et al (1997)
Author
Indications for ERCP
Type of pneumothorax
Female
Common bile duct stone
79
Female
9
59
2
Management
Outcome
Right
Chest tube insertion, laparotomy
Survived
Malignant obstructive jaundice
Bilateral
Bilateral chest tube insertion, laparotomy
Survived
Female
Common bile duct stone, postcholecystectomy
Right
Chest tube insertion
Survived
80
Female
Biliary stricture
Right tension
Chest tube insertion, laparotomy
Survived
10
89
Female
Acute cholecystitis
Right tension
Chest tube insertion
Survived
Lagoudianakis et al (2006)
1
55
Male
Gall bladder stones with jaundice
Right
Conservative only
Survived
Markogiannakis et al (2007)
5
56
Female
Acute cholecystitis, biliary obstruction
Bilateral
Bilateral chest tube insertion
Survived
Han et al (2008)
6
63
Male
Gall bladder stones with jaundice
Right tension
Chest tube insertion, laparotomy
Survived
Song et al (2009)
4
78
Female
Acute cholecystitis, biliary obstruction
Right tension
Chest tube insertion
Died
Ferrara et al (2009)
3
82
Male
Acute cholecystitis, biliary obstruction
Left
Chest tube insertion
Survived
25
Female
Acute cholecystitis, biliary obstruction
Right tension
Chest tube insertion, laparotomy
Survived
Hui et al (2001)
Present case (2010)
48
ASIAN JOURNAL OF SURGERY VOL 34 • NO 1 • JANUARY 2011
■ TENSION PNEUMOTHORAX COMPLICATING ERCP ■
The treatment of patients with suspected perforation of the duodenum associated with pneumothorax following ERCP remains controversial. The presence of a pneumothorax after ERCP is not a clear indication for surgical intervention.1 Most of the patients (6 patients) could be treated conservatively by chest drainage, nasogastric tube suction, and broad spectrum antibiotics.10 In patients with a deteriorating clinical picture or having continuous duodenal leakage confirmed by contrast studies, immediate laparotomy is essential. The delay in the diagnosis or operative intervention for such patients has a high morbidity and mortality.4,9 In contrast, in the five patients who had tension pneumothorax in Table 1, three (60%) needed laparotomy, and one, who refused surgery, died. In summary, tension pneumothorax with duodenal perforation is a rare complication of ERCP. It occurs mainly in the right side of the chest. The clinician should be aware of this serious complication. Unexplained chest pain, dyspnoea, and oxygen desaturation with abdominal distension during ERCP must raise this possibility. Early clinical recognition and prompt management is essential to improve the outcome.
References 1. Lagoudianakis EE, Tsekouras D, Papadima A, et al. Pneumothorax complicating endoscopic sphincterotomy successfully treated conservatively. Acta Gastroenterol Belg 2006;69:342–4.
ASIAN JOURNAL OF SURGERY VOL 34 • NO 1 • JANUARY 2011
2. Morley AP, Lau JY, Young RJ. Tension pneumothorax complicating a perforation of a duodenal ulcer during ERCP with endoscopic sphincterotomy. Endoscopy 1997;29:332. 3. Ferrara F, Luigiano C, Billi P, et al. Pneumothorax, pneumomediastinum, pneumoperitoneum, pneumoretroperitoneum, and subcutaneous emphysema after ERCP. Gastrointest Endosc 2009; 69:1398–401. 4. Song SY, Lee KS, Na KJ, et al. Tension pneumothorax after endoscopic retrograde pancreatocholangiogram. J Korean Med Sci 2009;24:173–5. 5. Markogiannakis H, Toutouzas KG, Pararas NV, et al. Bilateral pneumothorax following endoscopic retrograde cholangiopancreatography: a case report. Endoscopy 2007;39(Suppl 1):E195. 6. Han ML, Wu YM, Liu KL, et al. Tension pneumothorax after an ERCP in a patient with hepatic hydrothorax and sealed-off perforated duodenal ulcer. Gastrointest Endosc 2008;68:771–2. 7. Savides T, Sherman S, Kadell B, et al. Bilateral pneumothoraces and subcutaneous emphysema after endoscopic sphincterotomy. Gastrointest Endosc 1993;39:814–7. 8. Gya D, Sali A, Angus D. Subcutaneous emphysema and pneumothorax following endoscopic sphincterotomy. Aust N Z J Surg 1989;59:900–2. 9. Scarlett PY, Falk GL. The management of perforation of the duodenum following endoscopic sphincterotomy: a proposal for selective therapy. Aust N Z J Surg 1994;64:843–6. 10. Hui CK, Lai KC, Yuen MF, et al. Tension pneumothorax complicating ERCP in a patient with a Billroth II gastrectomy. Gastrointest Endosc 2001;54:254–6. 11. Mosler P, Fogel EL. Massive subcutaneous emphysema after attempted endoscopic retrograde cholangiopancreatography in a patient with a history of bariatric gastric bypass surgery. Endoscopy 2007;39(Suppl 1):E155.
49