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Continuous neostigmine infusion versus bolus neostigmine in refractory Ogilvie syndrome
American Journal of Emergency Medicine (2011) 29, 576.e1–576.e3
www.elsevier.com/locate/ajem
Case Report Continuous neostigmine infusion versus bolus neostigmine in refractory Ogilvie syndrome Abstract Acute colonic pseduo-obstruction (ACPO), or Ogilvie syndrome, is a syndrome of colonic obstructive symptoms and dilatation in the confirmed absence of mechanical obstruction. It carries a high mortality, which increases with the duration of the disease. Because the pathophysiology is thought to involve an excess of sympathetic activation with parasympathetic inhibition, the acetylcholinesterase inhibitor neostigmine has replaced surgical management as the primary mode of therapy. The optimal dose, rate, and frequency of neostigmine administration remain largely unexplored. Our patient had ACPO that was refractory to traditional bolus dosing of neostigmine. A continuous infusion of 0.4 mg/h (5 mg neostigmine in 50 mL of 0.9% normal sline) was therefore started in an intensive care setting. Bowel sounds returned and 8 hours later he passed stool and flatus. Though the infusion was discontinued, the bowel sounds remained persistent and complete resolution of pseduo-obstruction occurred. The likely mechanism of a superior response to continuous infusion is probably related to the short mean half-life (1 hour) of neostigmine. A continuous infusion would likely lead to prolonged period of sustained and subdued peristalsis resulting in the resolution of nonobstructive ileus that is otherwise refractory to bolus doses of neostigmine. Continuous neostigmine infusion may thus be tried in ACPO patients who are refractory to bolus doses of neostigmine. Acute colonic pseduo-obstruction (ACPO), or Ogilvie syndrome, is a syndrome of colonic dilatation with obstructive symptoms in the absence of mechanical obstruction [1]. Although the use of neostigmine for ACPO has become a first-line therapy, the optimal dose, frequency, and duration of administration have remained largely unexplored [1]. A 52-year-old man with a history of heavy alcohol use and known cirrhotic portal hypertension with a history of banded varices presented to the emergency department with 1 day of recurrent hematemesis. An emergent endoscopy 0735-6757/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
revealed gastric varices with brisk, spurting bleeding. He was transferred to the intensive care unit (ICU); continuous esomeprazole and octreotide infusions were initiated. Abdominal computed tomography (CT) performed on admission revealed a cirrhotic liver and portal hypertension but no abnormal bowel findings. On the second day of admission, a transjugular intrahepatic portosystemic shunt was performed. In the 15 hours between his admission to the ICU and execution of transjugular intrahepatic portosystemic shunt, the patient had 2 large, dark-red bowel movements. For approximately 5 days afterward, he passed only small amounts of melena twice. He received 4 days of standing lactulose with no improvement in his abdominal examination or cecal distention. Hypokalemia and hypophosphatemia were aggressively corrected over this time. By postoperative day 6, the patient had developed a grossly distended abdomen with absent bowel sounds that correlated with a colonic ileus on abdominal plain films. This ileus was confirmed to be nonobstructive by an abdominal CT scan. Upon confirming that his ileus was nonobstructive, 2.5 mg of intravenous neostigmine was infused over 3 minutes. Immediately after the infusion, the patient's bowel sounds were restored and he passed a large amount of liquid brown stool. His abdomen, however, remained distended, and bowel sounds vanished shortly afterward. Two additional infusions of neostigmine 6 and 14 hours after the first dose were performed without any significant improvement. Twenty hours after the first infusion of neostigmine, the patient's abdomen had become markedly more distended. Surgery and gastroenterology were consulted and recommended against operative intervention due to the high risk of mortality. A continuous neostigmine infusion was prepared according to the protocol described by Van der Spoel et al [2]. Neostigmine 5 mg in 50 mL of normal saline (0.9%) was administered by continuous infusion at 0.4 mg/h under continuous telemetry. Bowel sounds returned slowly but remained sustained, and 8 hours after the initiation of the infusion (with a total of 2.4 mg neostigmine infused), the patient passed a small amount of stool and flatus.
576.e2
Case Report
Fig. 1 A, Abdominal scout CT on day 6 of hospitalization and before the first administration of bolus neostigmine, showing cecal distension of approximately 10 cm. No obstruction was noted. B, Abdominal CT suggestive of nonobstructive cecal distension.
The infusion was discontinued, and the patient's bowel sounds remained persistent. The next day, he had 3 bowel movements and frequent passage of flatus with no administration of additional prokinetics. In the subsequent day, he had 5 bowel movements with dramatic improvement in his abdominal distention. He was transferred out of the ICU, where this clinical improvement persisted to complete resolution of his colonic ileus with no further prokinetic administration. He was discharged home 14 days after admission (Fig. 1). The pathologic mechanism of ACPO is postulated to be due to an excess of sympathetic involvement and of parasympathetic inhibition [2]. Therefore, the potentiation of parasympathetic action with neostigmine has gained acceptance as the treatment of choice for ACPO [2,3]. Administration by slow bolus is generally recommended [3]. Bronchospasm and bradycardia are the most common adverse effects, and therefore, the administration should be under an intensive care setting [4]. In contrast, a retrospective analysis of 400 cases of ACPO between 1970 and 1985 found a mortality of 13% in those patients undergoing endoscopic decompression and 30% undergoing surgery [5]. Although neostigmine has achieved ascendance as a modality of treatment, the method of administration has remained largely uninvestigated. The predominance of studies involving neostigmine and ACPO has used a protocol in which either 2 or 2.5 mg of neostigmine was given between 1 and 5 minutes. Only 1 study by Van der Spoel et al [2] used a protocol involving a continuous neostigmine infusion. Furthermore, there is no study comparing the role of continuous infusion after the failure of bolus infusions of neostigmine. Our patient clinically deteriorated despite
repeated boluses of neostigmine yet who maintained a sustained and ultimately curative response to a slow infusion of neostigmine over several hours. Although the mechanism of improved response to the continuous infusion is unclear, it can be hypothesized that this is tied to neostigmine's short duration of action [6]. Because the mean half-life is approximately an hour, it is possible that rather than a brief period of explosive peristalsis, a prolonged period of sustained and subdued peristalsis may, in select cases of nonobstructive ileus, be more successful while at the same time be less prone to the already-rare adverse effects of the drug. In conclusion, continuous neostigmine infusion should be tried in ACPO patients who are refractory to bolus doses of neostigmine, before exploring invasive treatment options. Luke White DO Gagangeet Sandhu MD Department of Internal Medicine St. Luke's - Roosevelt Hospital Center Columbia University College of Physicians and Surgeons New York, NY E-mail address: [email protected] doi:10.1016/j.ajem.2010.06.006
References [1] Saunders MD. Acute colonic pseudo-obstruction. Gastrointest Endosc Clin N Am 2007;17(2):341-60. [2] Van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP, Bosman RJ, Zandstra DF. Neostigmine resolves critical illness-related colonic ileus
Case Report in intensive care patients with multiple organ failure- a prospective, doubleblind, placebo-controlled trial. Intensive Care Med 2001;27(5):822-7. [3] De Giorgio R, Knowles CH. Acute colonic pseudo-obstruction. Br J Surg 2009;96(3):229-39. [4] Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med 1999;341(3):137-41.
576.e3 [5] Vanek VW, Al-Salti M. Acute pseudo-obstruction of the colon (Ogilvie's syndrome). An analysis of 400 cases. Dis Colon Rectum 1986;29(3):203-10. [6] Hartvig P, Wiklund L, Aquilonius SM, Lindström B. Clinical pharmacokinetics of acetylcholinesterase inhibitors. Prog Brain Res 1990;84:139-43.
www.elsevier.com/locate/ajem
Case Report Continuous neostigmine infusion versus bolus neostigmine in refractory Ogilvie syndrome Abstract Acute colonic pseduo-obstruction (ACPO), or Ogilvie syndrome, is a syndrome of colonic obstructive symptoms and dilatation in the confirmed absence of mechanical obstruction. It carries a high mortality, which increases with the duration of the disease. Because the pathophysiology is thought to involve an excess of sympathetic activation with parasympathetic inhibition, the acetylcholinesterase inhibitor neostigmine has replaced surgical management as the primary mode of therapy. The optimal dose, rate, and frequency of neostigmine administration remain largely unexplored. Our patient had ACPO that was refractory to traditional bolus dosing of neostigmine. A continuous infusion of 0.4 mg/h (5 mg neostigmine in 50 mL of 0.9% normal sline) was therefore started in an intensive care setting. Bowel sounds returned and 8 hours later he passed stool and flatus. Though the infusion was discontinued, the bowel sounds remained persistent and complete resolution of pseduo-obstruction occurred. The likely mechanism of a superior response to continuous infusion is probably related to the short mean half-life (1 hour) of neostigmine. A continuous infusion would likely lead to prolonged period of sustained and subdued peristalsis resulting in the resolution of nonobstructive ileus that is otherwise refractory to bolus doses of neostigmine. Continuous neostigmine infusion may thus be tried in ACPO patients who are refractory to bolus doses of neostigmine. Acute colonic pseduo-obstruction (ACPO), or Ogilvie syndrome, is a syndrome of colonic dilatation with obstructive symptoms in the absence of mechanical obstruction [1]. Although the use of neostigmine for ACPO has become a first-line therapy, the optimal dose, frequency, and duration of administration have remained largely unexplored [1]. A 52-year-old man with a history of heavy alcohol use and known cirrhotic portal hypertension with a history of banded varices presented to the emergency department with 1 day of recurrent hematemesis. An emergent endoscopy 0735-6757/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
revealed gastric varices with brisk, spurting bleeding. He was transferred to the intensive care unit (ICU); continuous esomeprazole and octreotide infusions were initiated. Abdominal computed tomography (CT) performed on admission revealed a cirrhotic liver and portal hypertension but no abnormal bowel findings. On the second day of admission, a transjugular intrahepatic portosystemic shunt was performed. In the 15 hours between his admission to the ICU and execution of transjugular intrahepatic portosystemic shunt, the patient had 2 large, dark-red bowel movements. For approximately 5 days afterward, he passed only small amounts of melena twice. He received 4 days of standing lactulose with no improvement in his abdominal examination or cecal distention. Hypokalemia and hypophosphatemia were aggressively corrected over this time. By postoperative day 6, the patient had developed a grossly distended abdomen with absent bowel sounds that correlated with a colonic ileus on abdominal plain films. This ileus was confirmed to be nonobstructive by an abdominal CT scan. Upon confirming that his ileus was nonobstructive, 2.5 mg of intravenous neostigmine was infused over 3 minutes. Immediately after the infusion, the patient's bowel sounds were restored and he passed a large amount of liquid brown stool. His abdomen, however, remained distended, and bowel sounds vanished shortly afterward. Two additional infusions of neostigmine 6 and 14 hours after the first dose were performed without any significant improvement. Twenty hours after the first infusion of neostigmine, the patient's abdomen had become markedly more distended. Surgery and gastroenterology were consulted and recommended against operative intervention due to the high risk of mortality. A continuous neostigmine infusion was prepared according to the protocol described by Van der Spoel et al [2]. Neostigmine 5 mg in 50 mL of normal saline (0.9%) was administered by continuous infusion at 0.4 mg/h under continuous telemetry. Bowel sounds returned slowly but remained sustained, and 8 hours after the initiation of the infusion (with a total of 2.4 mg neostigmine infused), the patient passed a small amount of stool and flatus.
576.e2
Case Report
Fig. 1 A, Abdominal scout CT on day 6 of hospitalization and before the first administration of bolus neostigmine, showing cecal distension of approximately 10 cm. No obstruction was noted. B, Abdominal CT suggestive of nonobstructive cecal distension.
The infusion was discontinued, and the patient's bowel sounds remained persistent. The next day, he had 3 bowel movements and frequent passage of flatus with no administration of additional prokinetics. In the subsequent day, he had 5 bowel movements with dramatic improvement in his abdominal distention. He was transferred out of the ICU, where this clinical improvement persisted to complete resolution of his colonic ileus with no further prokinetic administration. He was discharged home 14 days after admission (Fig. 1). The pathologic mechanism of ACPO is postulated to be due to an excess of sympathetic involvement and of parasympathetic inhibition [2]. Therefore, the potentiation of parasympathetic action with neostigmine has gained acceptance as the treatment of choice for ACPO [2,3]. Administration by slow bolus is generally recommended [3]. Bronchospasm and bradycardia are the most common adverse effects, and therefore, the administration should be under an intensive care setting [4]. In contrast, a retrospective analysis of 400 cases of ACPO between 1970 and 1985 found a mortality of 13% in those patients undergoing endoscopic decompression and 30% undergoing surgery [5]. Although neostigmine has achieved ascendance as a modality of treatment, the method of administration has remained largely uninvestigated. The predominance of studies involving neostigmine and ACPO has used a protocol in which either 2 or 2.5 mg of neostigmine was given between 1 and 5 minutes. Only 1 study by Van der Spoel et al [2] used a protocol involving a continuous neostigmine infusion. Furthermore, there is no study comparing the role of continuous infusion after the failure of bolus infusions of neostigmine. Our patient clinically deteriorated despite
repeated boluses of neostigmine yet who maintained a sustained and ultimately curative response to a slow infusion of neostigmine over several hours. Although the mechanism of improved response to the continuous infusion is unclear, it can be hypothesized that this is tied to neostigmine's short duration of action [6]. Because the mean half-life is approximately an hour, it is possible that rather than a brief period of explosive peristalsis, a prolonged period of sustained and subdued peristalsis may, in select cases of nonobstructive ileus, be more successful while at the same time be less prone to the already-rare adverse effects of the drug. In conclusion, continuous neostigmine infusion should be tried in ACPO patients who are refractory to bolus doses of neostigmine, before exploring invasive treatment options. Luke White DO Gagangeet Sandhu MD Department of Internal Medicine St. Luke's - Roosevelt Hospital Center Columbia University College of Physicians and Surgeons New York, NY E-mail address: [email protected] doi:10.1016/j.ajem.2010.06.006
References [1] Saunders MD. Acute colonic pseudo-obstruction. Gastrointest Endosc Clin N Am 2007;17(2):341-60. [2] Van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP, Bosman RJ, Zandstra DF. Neostigmine resolves critical illness-related colonic ileus
Case Report in intensive care patients with multiple organ failure- a prospective, doubleblind, placebo-controlled trial. Intensive Care Med 2001;27(5):822-7. [3] De Giorgio R, Knowles CH. Acute colonic pseudo-obstruction. Br J Surg 2009;96(3):229-39. [4] Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med 1999;341(3):137-41.
576.e3 [5] Vanek VW, Al-Salti M. Acute pseudo-obstruction of the colon (Ogilvie's syndrome). An analysis of 400 cases. Dis Colon Rectum 1986;29(3):203-10. [6] Hartvig P, Wiklund L, Aquilonius SM, Lindström B. Clinical pharmacokinetics of acetylcholinesterase inhibitors. Prog Brain Res 1990;84:139-43.