572194
research-article2015
PENXXX10.1177/0148607115572194Journal of Parenteral and Enteral NutritionLodeserto et al
Case Report Journal of Parenteral and Enteral Nutrition Volume XX Number X Month 201X 1–3 © 2015 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607115572194 jpen.sagepub.com hosted at online.sagepub.com
Accidental Bolus of Parenteral Nutrition Frank Lodeserto, MD1; Mohammed al-Jaghbeer, MD1; and David Huang, MD, MPH1,2
Abstract There is a paucity of data that exists regarding acute toxicity and management in the setting of parental nutrition (PN) overdose. We describe a case of a patient who received an accidental rapid bolus of PN and fat emulsion. She developed a seizure, metabolic acidosis, arrhythmias, myocardial ischemia, altered mental status, hypotension, and hypoxemia likely caused by elevated triglycerides, leading to a hyperviscosity syndrome. After failing standard therapy, she was successfully treated with a single-volume plasma exchange with resolution of symptoms. Fat emulsion or intravenous lipid emulsion and much of its safety have been recently described in its use as a rescue therapy in resuscitation from drug-related toxicity. Elevated serum triglyceride levels can result in a picture similar to a hyperviscosity syndrome. Plasma exchange is a known therapeutic modality for the management of hyperviscosity syndrome and a novel therapy in the treatment of hyperviscosity syndrome due to fat emulsion therapy. In a patient receiving PN with development of rapid deterioration of clinical status, without an obvious etiology, there should be consideration of PN overdose. A rapid assessment and treatment of severe electrolyte abnormalities should be undertaken immediately to prevent life-threatening cardiovascular and central nervous system collapse. If fat emulsion was rapidly coadministered and there are signs and symptoms of hyperviscosity syndrome, then consideration should be given to plasma exchange as an effective therapeutic treatment option. (JPEN J Parenter Enteral Nutr. XXXX;xx:xx-xx)
Keywords accidental PN bolus; Intralipid; plasma exchange
The use of parenteral nutrition (PN) in adults is indicated when enteral nutrition (EN) is unable to be initiated or tolerated, particularly in the setting of a nonfunctional gastrointestinal (GI) tract. It is classified as a high-alert medication1 due to the risk of electrolyte and mineral compounding errors during its production and metabolic derangements that may arise as a result of its use.2 Hence, multiple guidelines have been devised to standardize practice for patient safety.3 There is a paucity of data that exists in the literature regarding accidental bolus of PN leading to severe metabolic derangements. Most of the cases reported have occurred in neonates and have occurred as a result of compounding errors in its production. We are reporting a case of an accidental bolus of PN and fat emulsion in a 69-year-old woman and the ensuing treatment with limited published data.
realized by the nursing staff that she was inadvertently bolused with 1200 mL of her 1800-mL PN dose as well as 200 mL of fat emulsion in less than 1 hour. The medical team focused on correction of possible severe electrolyte and metabolic abnormalities caused by the rapid infusion of PN. She was treated empirically for hyperkalemia prior to a bedside arterial blood gas sampling, which revealed a severe combined metabolic and respiratory acidosis (6.99/64/78/15/97/–17), lactic acidosis (lactate, 11.8 mmol/L), hyperglycemia (glucose, 775 mg/dL), and a mild hyperkalemia (potassium, 5.0 mmol/L). One hour after her seizure, her mental status remained depressed; she remained in atrial fibrillation and began to develop myocardial ischemia as well as hypotension and
Case
From the 1Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; and 2The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
We present a case of a 69-year-old (44 kg) woman, with a prolonged hospital stay after initially being admitted with a myocardial infarction. Her hospital course was complicated by the development of intestinal ischemia requiring a significant bowel resection leading to short gut syndrome and the need for PN. Several days after the initiation of PN, she developed a new-onset seizure, hyperglycemia, atrial fibrillation, and respiratory failure requiring mechanical ventilation. After initially stabilizing her medical condition, she was brought to the intensive care unit (ICU) for further management. It was quickly
Financial disclosure: None declared. Received for publication November 13, 2014; accepted for publication January 7, 2015. Corresponding Author: Frank Lodeserto, MD, Pediatric Critical Care Medicine, Children’s Hospital of Pittsburgh of UPMC, Suite 02000, Faculty Pavilion, 4401 Penn Ave, Pittsburgh, PA 15224, USA. Email: [email protected]
Downloaded from pen.sagepub.com at Bobst Library, New York University on November 17, 2015
2
Journal of Parenteral and Enteral Nutrition XX(X)
required the use of vasopressors. In addition, she developed severe hypoxemia requiring full mechanical ventilator support and 100% fraction of inspired oxygen (FiO2) and escalating positive end-expiratory pressure (PEEP). During the next 2 hours there was very little change in the patient’s clinical status. The medical team obtained a head computed tomography (CT) scan, which did not show any acute abnormalities, and an electroencephalogram (EEG) that demonstrated diffuse slowing consistent with a metabolic encephalopathy, without evidence of seizures. The patient’s laboratory values were reportedly lipemic and unable to be measured by the hospital laboratory after multiple attempts. She remained unresponsive despite attempts to reverse her underlying abnormalities. An immediate literature search failed to reveal any relevant case reports of accidental PN infusions. After attempting to correct her electrolytes and acidosis with an insulin infusion, bicarbonate, and intravenous fluids, we became suspicious of a possible hyperviscosity syndrome from hypertriglyceridemia caused by the 200 mL of fat emulsion she received along with the PN bolus. The team’s suspicion was heightened as several attempts to collect laboratory values were unsuccessful due hypertriglyceridemia. Without literature to guide our therapy, our team consulted a number of specialists, including our hospital’s pediatric intensive care team, which recommended a trial of plasma exchange to lower her triglycerides caused by the rapid fat emulsion bolus. After a single-volume plasma exchange, our patient’s hypoxemia, myocardia ischemia, and mental status improved. A few hours following therapy, a repeat ECG showed resolution of her ST depressions; she was weaned off mechanical ventilation, and she returned to her baseline neurologic status.
Discussion PN remains a widely used therapy but has been associated with various side effects related to electrolyte derangements, compounding errors of electrolytes and minerals during its production, infections, hyperglycemia, hyperlipidemia, and others.2,4 Currently, there is very limited published literature to guide the management of rapid accidental infusions of PN. The reason for a lack of literature is because it rarely occurs or is not reported by clinicians, since it is a negative event, which, in general, is less likely to be reported in the literature. PN is often but not always accompanied by fat emulsion, which has been recently described in its use as a rescue therapy in resuscitation from drug-related toxicity.5 Fat emulsion or intravenous lipid emulsion (ILE) has been used successfully as an antidote to reverse the effects of lipophilic toxic agents that have caused cardiac arrest and severe central nervous system (CNS) embarrassment.5 The proposed mechanism is that it works as a “lipid sink” and acts to sequester the lipophilic toxin and reduce its toxicity. The recommended ILE dose in the setting of cardiac arrest or CNS depression from lipophilic toxin agents is 1.5 mL/kg
infused over 1 minute followed by continuous infusion (approximately 0.25–0.5 mL/kg/min) for 10 minutes. Much higher doses of ILE (>4 mL/kg) have been used safely in case reports to successfully resuscitate patients in cardiac arrest, but its safety and upper limit of dosing have yet to be established. Our patient (44 kg) received 200 mL of ILE that was >4.5 mL/kg, and although doses >4 mL/kg have been described in case reports, this dose is still considered at the extremes of dosing for ILE. The limitations of the use of ILE as an antidote are restricted to case reports, and no large randomized controlled trial has been undertaken to clearly define the safety of ILE as well as the safe range for dosing. Another restriction of ILE therapy is that nearly all of the case reports are positive results, and negative case reports discussing ILE are lacking. The side effects of emulsion are related to the dose and rate of administration.6 High doses of lipid in the serum can result in a picture similar to hyperviscosity syndrome or fat overload syndrome, which was reported before as a complication of PN.7 Symptoms can include decreased cerebral blood flow, altered mental status, acute respiratory failure, and decreased coronary perfusion resulting in cardiac ischemia. Plasma exchange is a known therapeutic modality for the management of hyperviscosity syndrome8 and a novel therapy in the treatment of fat overload syndrome due to fat emulsion therapy.9 This case proposed a number of challenges related to the uncertainty of the etiology of her comatose state and prolonged hypoxemia and cardiac ischemia. The diagnosis could have perhaps been secondary to the infusion of PN, causing rapid electrolyte abnormalities leading to seizure and arrhythmia. Perhaps the seizure accompanied by a prolonged postictal state as well as the treatment with a benzodiazepine, a known CNS depressant, may have contributed to her unresponsiveness. Cardiac ischemia may have been caused by supply-demand mismatch due to her atrial fibrillation with a rapid ventricular rate. However, despite our management of this patient’s electrolyte and acid base abnormalities and a period of observation, her lack of clinical improvement accompanied with hypertriglyceridemia made the diagnosis of hyperviscosity syndrome seem likely. Hyperviscosity syndrome would explain impaired cerebellar, pulmonary, and coronary blood flow, leading to altered mental status, hypoxemia, and cardiac ischemia, especially in our patient with known vascular and coronary insufficiency. After a single-volume plasma exchange, we observed a rapid resolution in her coronary ischemia, near-immediate return to her baseline mental status, and liberation from mechanical ventilation, requiring only slightly higher FiO2 from before her seizure.
Summary In a patient receiving PN with the development of rapid deterioration of clinical status, in addition to the standard workup, PN overdose should be included in the differential diagnosis.
Downloaded from pen.sagepub.com at Bobst Library, New York University on November 17, 2015
Lodeserto et al
3
A rapid assessment and treatment of severe electrolyte abnormalities should be undertaken immediately if PN bolus is suspected to prevent life-threatening cardiovascular and CNS effects. If fat emulsion was rapidly coadministered and there are signs and symptoms of hypertriglyceridemia and hyperviscosity syndrome, then consideration should be given to plasma exchange as a novel therapeutic treatment. When the literature is either lacking or absent, it is important to draw on the knowledge and experience of multiple resources from various fields to help guide medical therapy.
References 1. Institute for Safe Medication Practices. ISMP’s list of high-alert medications, 2012. http://www.ismp.org/Tools/highalertmedications.pdf. Accessed February 17, 2014. 2. Ukleja A, Romano MM. Complications of parenteral nutrition. Gastroenterol Clin North Am. 2007;36:23-46.
3. Ayers P, Adams S, Boullata J, et al. A.S.P.E.N. parenteral nutrition safety consensus recommendations. JPEN J Parenter Enteral Nutr. 2014;38(3):296-333. 4. Lauriti G, Zani A, Aufieri R, et al. Incidence, prevention, and treatment of parenteral nutrition–associated cholestasis and intestinal failure–associated liver disease in infants and children: a systematic review. JPEN J Parenter Enteral Nutr. 2014;38(1):70-85. 5. Martillo JM, Dasta JF, Kleinschmidt KC, Varon J. State of the art review: intravenous fat emulsions: current applications, safety profile, and clinical implications. Ann Phamacother. 2010;44:688-700. 6. Driscoll DF. Lipid injectable emulsions. Nutr Clin Pract. 2006;21: 381-386. 7. Heyman MB, Storch S, Ament ME. The fat overload syndrome: report of a case and literature review. Am J Dis Child. 1981;135:628-670. 8. Gertz MA, Kyle RA. Hyperviscosity syndrome. J Intensive Care Med. 1995;10:128-141. 9. Kollef MH, McCormack MT, Caras WE, Reddy VV, Bacon D. The fat overload syndrome: successful treatment with plasma exchange. Ann Intern Med. 1990;112(7):545-546.
Downloaded from pen.sagepub.com at Bobst Library, New York University on November 17, 2015
research-article2015
PENXXX10.1177/0148607115572194Journal of Parenteral and Enteral NutritionLodeserto et al
Case Report Journal of Parenteral and Enteral Nutrition Volume XX Number X Month 201X 1–3 © 2015 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607115572194 jpen.sagepub.com hosted at online.sagepub.com
Accidental Bolus of Parenteral Nutrition Frank Lodeserto, MD1; Mohammed al-Jaghbeer, MD1; and David Huang, MD, MPH1,2
Abstract There is a paucity of data that exists regarding acute toxicity and management in the setting of parental nutrition (PN) overdose. We describe a case of a patient who received an accidental rapid bolus of PN and fat emulsion. She developed a seizure, metabolic acidosis, arrhythmias, myocardial ischemia, altered mental status, hypotension, and hypoxemia likely caused by elevated triglycerides, leading to a hyperviscosity syndrome. After failing standard therapy, she was successfully treated with a single-volume plasma exchange with resolution of symptoms. Fat emulsion or intravenous lipid emulsion and much of its safety have been recently described in its use as a rescue therapy in resuscitation from drug-related toxicity. Elevated serum triglyceride levels can result in a picture similar to a hyperviscosity syndrome. Plasma exchange is a known therapeutic modality for the management of hyperviscosity syndrome and a novel therapy in the treatment of hyperviscosity syndrome due to fat emulsion therapy. In a patient receiving PN with development of rapid deterioration of clinical status, without an obvious etiology, there should be consideration of PN overdose. A rapid assessment and treatment of severe electrolyte abnormalities should be undertaken immediately to prevent life-threatening cardiovascular and central nervous system collapse. If fat emulsion was rapidly coadministered and there are signs and symptoms of hyperviscosity syndrome, then consideration should be given to plasma exchange as an effective therapeutic treatment option. (JPEN J Parenter Enteral Nutr. XXXX;xx:xx-xx)
Keywords accidental PN bolus; Intralipid; plasma exchange
The use of parenteral nutrition (PN) in adults is indicated when enteral nutrition (EN) is unable to be initiated or tolerated, particularly in the setting of a nonfunctional gastrointestinal (GI) tract. It is classified as a high-alert medication1 due to the risk of electrolyte and mineral compounding errors during its production and metabolic derangements that may arise as a result of its use.2 Hence, multiple guidelines have been devised to standardize practice for patient safety.3 There is a paucity of data that exists in the literature regarding accidental bolus of PN leading to severe metabolic derangements. Most of the cases reported have occurred in neonates and have occurred as a result of compounding errors in its production. We are reporting a case of an accidental bolus of PN and fat emulsion in a 69-year-old woman and the ensuing treatment with limited published data.
realized by the nursing staff that she was inadvertently bolused with 1200 mL of her 1800-mL PN dose as well as 200 mL of fat emulsion in less than 1 hour. The medical team focused on correction of possible severe electrolyte and metabolic abnormalities caused by the rapid infusion of PN. She was treated empirically for hyperkalemia prior to a bedside arterial blood gas sampling, which revealed a severe combined metabolic and respiratory acidosis (6.99/64/78/15/97/–17), lactic acidosis (lactate, 11.8 mmol/L), hyperglycemia (glucose, 775 mg/dL), and a mild hyperkalemia (potassium, 5.0 mmol/L). One hour after her seizure, her mental status remained depressed; she remained in atrial fibrillation and began to develop myocardial ischemia as well as hypotension and
Case
From the 1Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; and 2The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
We present a case of a 69-year-old (44 kg) woman, with a prolonged hospital stay after initially being admitted with a myocardial infarction. Her hospital course was complicated by the development of intestinal ischemia requiring a significant bowel resection leading to short gut syndrome and the need for PN. Several days after the initiation of PN, she developed a new-onset seizure, hyperglycemia, atrial fibrillation, and respiratory failure requiring mechanical ventilation. After initially stabilizing her medical condition, she was brought to the intensive care unit (ICU) for further management. It was quickly
Financial disclosure: None declared. Received for publication November 13, 2014; accepted for publication January 7, 2015. Corresponding Author: Frank Lodeserto, MD, Pediatric Critical Care Medicine, Children’s Hospital of Pittsburgh of UPMC, Suite 02000, Faculty Pavilion, 4401 Penn Ave, Pittsburgh, PA 15224, USA. Email: [email protected]
Downloaded from pen.sagepub.com at Bobst Library, New York University on November 17, 2015
2
Journal of Parenteral and Enteral Nutrition XX(X)
required the use of vasopressors. In addition, she developed severe hypoxemia requiring full mechanical ventilator support and 100% fraction of inspired oxygen (FiO2) and escalating positive end-expiratory pressure (PEEP). During the next 2 hours there was very little change in the patient’s clinical status. The medical team obtained a head computed tomography (CT) scan, which did not show any acute abnormalities, and an electroencephalogram (EEG) that demonstrated diffuse slowing consistent with a metabolic encephalopathy, without evidence of seizures. The patient’s laboratory values were reportedly lipemic and unable to be measured by the hospital laboratory after multiple attempts. She remained unresponsive despite attempts to reverse her underlying abnormalities. An immediate literature search failed to reveal any relevant case reports of accidental PN infusions. After attempting to correct her electrolytes and acidosis with an insulin infusion, bicarbonate, and intravenous fluids, we became suspicious of a possible hyperviscosity syndrome from hypertriglyceridemia caused by the 200 mL of fat emulsion she received along with the PN bolus. The team’s suspicion was heightened as several attempts to collect laboratory values were unsuccessful due hypertriglyceridemia. Without literature to guide our therapy, our team consulted a number of specialists, including our hospital’s pediatric intensive care team, which recommended a trial of plasma exchange to lower her triglycerides caused by the rapid fat emulsion bolus. After a single-volume plasma exchange, our patient’s hypoxemia, myocardia ischemia, and mental status improved. A few hours following therapy, a repeat ECG showed resolution of her ST depressions; she was weaned off mechanical ventilation, and she returned to her baseline neurologic status.
Discussion PN remains a widely used therapy but has been associated with various side effects related to electrolyte derangements, compounding errors of electrolytes and minerals during its production, infections, hyperglycemia, hyperlipidemia, and others.2,4 Currently, there is very limited published literature to guide the management of rapid accidental infusions of PN. The reason for a lack of literature is because it rarely occurs or is not reported by clinicians, since it is a negative event, which, in general, is less likely to be reported in the literature. PN is often but not always accompanied by fat emulsion, which has been recently described in its use as a rescue therapy in resuscitation from drug-related toxicity.5 Fat emulsion or intravenous lipid emulsion (ILE) has been used successfully as an antidote to reverse the effects of lipophilic toxic agents that have caused cardiac arrest and severe central nervous system (CNS) embarrassment.5 The proposed mechanism is that it works as a “lipid sink” and acts to sequester the lipophilic toxin and reduce its toxicity. The recommended ILE dose in the setting of cardiac arrest or CNS depression from lipophilic toxin agents is 1.5 mL/kg
infused over 1 minute followed by continuous infusion (approximately 0.25–0.5 mL/kg/min) for 10 minutes. Much higher doses of ILE (>4 mL/kg) have been used safely in case reports to successfully resuscitate patients in cardiac arrest, but its safety and upper limit of dosing have yet to be established. Our patient (44 kg) received 200 mL of ILE that was >4.5 mL/kg, and although doses >4 mL/kg have been described in case reports, this dose is still considered at the extremes of dosing for ILE. The limitations of the use of ILE as an antidote are restricted to case reports, and no large randomized controlled trial has been undertaken to clearly define the safety of ILE as well as the safe range for dosing. Another restriction of ILE therapy is that nearly all of the case reports are positive results, and negative case reports discussing ILE are lacking. The side effects of emulsion are related to the dose and rate of administration.6 High doses of lipid in the serum can result in a picture similar to hyperviscosity syndrome or fat overload syndrome, which was reported before as a complication of PN.7 Symptoms can include decreased cerebral blood flow, altered mental status, acute respiratory failure, and decreased coronary perfusion resulting in cardiac ischemia. Plasma exchange is a known therapeutic modality for the management of hyperviscosity syndrome8 and a novel therapy in the treatment of fat overload syndrome due to fat emulsion therapy.9 This case proposed a number of challenges related to the uncertainty of the etiology of her comatose state and prolonged hypoxemia and cardiac ischemia. The diagnosis could have perhaps been secondary to the infusion of PN, causing rapid electrolyte abnormalities leading to seizure and arrhythmia. Perhaps the seizure accompanied by a prolonged postictal state as well as the treatment with a benzodiazepine, a known CNS depressant, may have contributed to her unresponsiveness. Cardiac ischemia may have been caused by supply-demand mismatch due to her atrial fibrillation with a rapid ventricular rate. However, despite our management of this patient’s electrolyte and acid base abnormalities and a period of observation, her lack of clinical improvement accompanied with hypertriglyceridemia made the diagnosis of hyperviscosity syndrome seem likely. Hyperviscosity syndrome would explain impaired cerebellar, pulmonary, and coronary blood flow, leading to altered mental status, hypoxemia, and cardiac ischemia, especially in our patient with known vascular and coronary insufficiency. After a single-volume plasma exchange, we observed a rapid resolution in her coronary ischemia, near-immediate return to her baseline mental status, and liberation from mechanical ventilation, requiring only slightly higher FiO2 from before her seizure.
Summary In a patient receiving PN with the development of rapid deterioration of clinical status, in addition to the standard workup, PN overdose should be included in the differential diagnosis.
Downloaded from pen.sagepub.com at Bobst Library, New York University on November 17, 2015
Lodeserto et al
3
A rapid assessment and treatment of severe electrolyte abnormalities should be undertaken immediately if PN bolus is suspected to prevent life-threatening cardiovascular and CNS effects. If fat emulsion was rapidly coadministered and there are signs and symptoms of hypertriglyceridemia and hyperviscosity syndrome, then consideration should be given to plasma exchange as a novel therapeutic treatment. When the literature is either lacking or absent, it is important to draw on the knowledge and experience of multiple resources from various fields to help guide medical therapy.
References 1. Institute for Safe Medication Practices. ISMP’s list of high-alert medications, 2012. http://www.ismp.org/Tools/highalertmedications.pdf. Accessed February 17, 2014. 2. Ukleja A, Romano MM. Complications of parenteral nutrition. Gastroenterol Clin North Am. 2007;36:23-46.
3. Ayers P, Adams S, Boullata J, et al. A.S.P.E.N. parenteral nutrition safety consensus recommendations. JPEN J Parenter Enteral Nutr. 2014;38(3):296-333. 4. Lauriti G, Zani A, Aufieri R, et al. Incidence, prevention, and treatment of parenteral nutrition–associated cholestasis and intestinal failure–associated liver disease in infants and children: a systematic review. JPEN J Parenter Enteral Nutr. 2014;38(1):70-85. 5. Martillo JM, Dasta JF, Kleinschmidt KC, Varon J. State of the art review: intravenous fat emulsions: current applications, safety profile, and clinical implications. Ann Phamacother. 2010;44:688-700. 6. Driscoll DF. Lipid injectable emulsions. Nutr Clin Pract. 2006;21: 381-386. 7. Heyman MB, Storch S, Ament ME. The fat overload syndrome: report of a case and literature review. Am J Dis Child. 1981;135:628-670. 8. Gertz MA, Kyle RA. Hyperviscosity syndrome. J Intensive Care Med. 1995;10:128-141. 9. Kollef MH, McCormack MT, Caras WE, Reddy VV, Bacon D. The fat overload syndrome: successful treatment with plasma exchange. Ann Intern Med. 1990;112(7):545-546.
Downloaded from pen.sagepub.com at Bobst Library, New York University on November 17, 2015
