Case Report

Access this article online Website: www.ijciis.org DOI: 10.4103/2229-5151.141487 Quick Response Code:

Intravenous colistin‑induced acute respiratory failure: A case report and a review of literature Amardeep Shrestha, Sheryll Mae Soriano1, Mingchen Song1, Shingo Chihara2

ABSTRACT The emergence of multi-drug-resistant gram negative bacillary infections has regained popularity of ancient drugs such as polymyxins. We report a case of acute respiratory failure induced by use of intravenous colistimethate, which is one of the forms of polymyxin. The patient is a 31 year old female with paraplegia due to spina bifida who underwent excisional debridement of large lumbosacral decubitus ulcer with osteomyelitis infected with pan-resistant Pseudomonas aeruginosa and MRSA. Six days after initiation of intravenous colistimethate and vancomycin, she developed acute respiratory failure requiring mechanical ventilation. Pan-culture was negative including a chest radiograph. V/Q scan showed low probability for pulmonary embolism. Echocardiogram showed normal right ventricle with no strain or pulmonary hypertension. Colistimethate was discontinued. Within 24 hours, she was extubated. In the early years after introduction of polymyxin, there were several reports of acute respiratory paralysis. The mechanism is thought to be noncompetitive myoneuronal presynaptic blockade of acetylcholine release. Though a direct causal relationship for respiratory failure is often difficult to establish in current era with multiple co morbidities, the timeframe of apnea, acuity of onset as well as rapid recovery in our case clearly point out the causal relationship. In addition, our patient also developed acute renal failure, presumably due to colistimethate induced nephrotoxicity, a possible contributing factor for her acute respiratory failure. In summary, colistimethate can induce acute neurotoxicity including respiratory muscular weakness and acute respiratory failure. Clinicians should consider its toxicity in the differential diagnosis of acute respiratory failure especially in critically ill patients.

Department of Internal Medicine, Division of General Internal Medicine, 1 Division of Pulmonary and Critical Care Medicine, 3Division of Infectious Diseases, Southern Illinois University School of Medicine, Springfield, Illinois, United States of America Address for correspondence: Dr. Amardeep Shrestha, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA. E‑mail: [email protected]

Key Words: Acute respiratory failure, colistin, neuromuscular blockade

INTRODUCTION Colistin belongs to the polymyxin class of antibiotics which is a group of cationic polypeptides.[1] Polymyxins were in clinical use during the 1960s after introduction in 1947. However, the popularity rapidly faded in 1970s because of significant renal and neurological toxicity and was replaced with less toxic antibiotics with a comparable or broader antibacterial spectrum such as aminoglycosides. [2] With the recent emergence of multi drug‑resistant (MDR) gram‑negative organisms, in particular Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumonia, colistin has been reconsidered as a potential therapeutic agent for the past 10‑15 years.[1] This has not only increased the clinical usage of this ancient drug, but has also increased the prevalence of all the toxicities related to colistin. 266

Neurotoxicity is the second most common toxicity after nephrotoxicity following colistin therapy. Among the various manifestations of its neurotoxicity, apnea and respiratory failure are of great concern. Several cases of respiratory failure due to colistin were reported in the previous era. However, this has not been seen commonly since its reintroduction. We report a case of acute respiratory failure induced by intravenous use of colistin.

CASE REPORT A 31‑year‑old white female with history of spina bifida, paraplegia, hydrocephalus status post ventriculo‑peritoneal shunt, osteomyelitis of the left

International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 3 | Jul-Sep 2014

Shrestha, et al.: Intravenous colistin‑induced acute respiratory failure

hip status post left leg amputation, and chronic sacral decubitus ulcer presented with foul smelling discharge from her sacral wound for 2 weeks. She underwent excisional debridement of her sacral wound. The culture from the wound grew two biotypes of Pseudomonas aeruginosa: One was resistant to all antibiotics except for colistin while the other was resistant to all antibiotics except for colistin and imipenem. In addition, methicillin‑resistant Staphylococcus aureus (MRSA) grew from the intraoperative bone culture. She was started on colistimethate sodium (CMS) 200 mg intravenously every 12 hours for her MDR P. aeruginosa. Intravenous vancomycin was used to treat MRSA. She was then discharged to a sub‑acute rehabilitation center on CMS and vancomycin. After three days, she was noted to have sudden respiratory distress in the sub‑acute rehabilitation center for which emergency medical service (EMS) was called. On arrival, she was noted to be unresponsive and having agonal breathing. She was immediately started on bag‑valve mask ventilation (BVM) and was taken to the emergency room (ER). In the ER, she was noted to have oxygen saturation at 80s on BVM and was emergently intubated. Shortly after resuscitation, her arterial blood gas analysis revealed pH of 7.45, PaCO2 of 25, and PaO2 of 280 mmHg (on FiO2 of 100%). Her labs were significant for leukocytosis with white cell count of 20,000/mm 3 and an acutely elevated creatinine of 2.2 mg/dL (baseline creatinine was 0.9 mg/dl at the time of discharge) with metabolic acidosis with bicarbonate of 18 mmol/L secondary to her renal failure. On further inquiry, there was no exposure to any narcotics or muscle relaxants that might have contributed to her respiratory depression. She was in a supervised unit prior to the presentation, which deterred the possibility of any toxic exposure to the patient. Two sets of blood cultures were negative while the wound culture revealed the same biotypes of MDR P. aeruginosa. Chest radiograph did not reveal any parenchymal abnormalities. Neurological workup was unrevealing and ventilation/perfusion scan (V/Q scan) for pulmonary embolism was low probability. Venous duplex of her lower extremity revealed a chronic posterior tibial vein thrombus. An echocardiogram showed normal right ventricle with no strain or pulmonary hypertension. Colistin was stopped as it was thought to be the cause of renal failure and respiratory failure and the patient was started on imipenem. She was extubated within 24 hours. Her creatinine peaked at 3.7 mg/dl and she did not require hemodialysis. Her respiratory and neurological status remained stable during hospitalization and tolerated imipenem and vancomycin for her osteomyelitis and chronic decubitus ulcer infection. She was discharged after one week.

DISCUSSION Our patient developed acute respiratory failure requiring intubation and mechanical ventilation 6 days after initiation of colistin. Respiratory muscle paralysis, as depicted, is one of the manifestations of the neurotoxic effect of colistin. The cases were reported mostly between 1964 and 1973 [Table 1]. We applied the Naranjo adverse drug reaction probability scale to our case, which indicated a probable relationship. The case is limited with the unavailability of arterial blood gas prior to the event as she was emergently intubated on presentation. Also, since colistin is reserved for severely ill patients with multiple co‑morbidities, it may be difficult to establish direct causal relationship for acute respiratory failure and colistin. Colistin was most likely to be the culprit of her respiratory failure from the timing of apnea as well as rapid recovery after stopping colistin. Acute renal failure leading to presumed high concentration of serum colistin may be another contributory factor for her respiratory failure. She had a chronic deep vein thrombus which is unlikely to cause acute respiratory failure since low probability for pulmonary embolism by V/Q scan and she recovered within 24 hours without any intervention. Colistin is also called polymyxin E and is a part of polymyxin family which is a group of polypeptide antibiotics. It exerts its bactericidal effect by displacing the divalent cations magnesium and calcium, which stabilize anionic lipopolysaccharide molecules in the outer membrane of gram‑negative bacteria. This disrupts the cell permeability and ultimately leads to cell death.[1] It was initially introduced in 1949 and was in clinical use in 1960s. However, they were gradually abandoned in most parts of the world because of nephrotoxicity and neurotoxicity. The emergence of MDR gram negative bacteria led to the revival of polymyxins in more recent era as a valuable therapeutic option. In the last decade, intravenous polymyxins, particularly in the form of CMS, have been used to treat serious P. aeruginosa and A. baumannii infections of various types, including pneumonia, bacteremia, and urinary tract infections. The most common adverse effects of colistin therapy are nephrotoxicity and neurotoxicity. The major manifestations of colistin induced neurotoxicity include dizziness, weakness, facial and peripheral paresthesias, vertigo, visual disturbances, confusion, ataxia, and neuromuscular blockade. Koch‑Weser et al., reported the incidence of the neurotoxic manifestations to be about 7%, paresthesias being the most common.[14] The proposed mechanism is a non‑competitive myoneuronal presynaptic blockade of acetylcholine release, in contrast to the competitive blockade by most other antibiotics like neomycin, kanamycin, and streptomycin.[19]

International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 3 | Jul-Sep 2014

267

268 135 mg IV of polymyxin B 150 mg IM colistimethate

CMS IV 2.5 mg/kg q 12 hours 10 doses (IV); Unknown Inhaled CMS (75 mg nebulized q 6 doses 12 hours) (inhaled) a: Polymyxin 125 mg IV q 12 a: 1 a: 1 hour hours b: 4 b: 3 hours b: IV polymyxin B 200 mg loading dose then 80 mg IV q 72 hours

1 1 1

1

1

1

1

11

6

1 1

1

2

Perkins RL. 1964[6] Rapin, et al. 1965[7] Parisi and Kaplan. 1965[8]

Anthony and Louis. 1966[9]

Barlow and Groesbeer. 1966[10]

Pohlmann G. 1966[11]

Zauder, et al. 1966[12]

Lindesmith, et al. 1968[13]

Koch‑Weser, et al. 1970[14]

Colvard MC. 1971[15] Decker, Fincham, et al. 1971[16] Wahby, et al. 2010[17]

Wunsch, et al. 2012[18]

75 mg IM Twice daily (preoperative use) Colistin 100 mg BID IM to 150 mg IM BID 1 patient: Polymyxin B 50 mg IM 1 patient: Polymyxin B 100 mg IV CMS IM q 12 hours

1

1 1

Unknown

1‑29

17

7

1

11

7 45 17

1

5 hours 3 hours

Unknown

Apnea continued postoperatively 1 hour to 26 hours

2 hours

20 minutes

2‑3 hours

3.5 hours Unknown Unknown

Few minutes

Unknown

Small G. 1964[5]

Unknown

20 minutes

Duration of last dose to onset of apnea

1

1

No of doses

Fekety, et al. 1962[4]

Local Neosporin spray (150,000 units polymyxin B) Colistimethate IV 150 mg q 12 hours Intraperitoneal use of 100 mg of polymyxin B sulfate Colistin IM 150 mg twice daily Colistin 10,000,000 units/day CMS 150 mg IM×twice daily×8 days Colistin 100 mg IM three times daily Local Neosporin spray during surgery (100,000 units of polymyxin B sulphate) Polymyxin B IV 25 mg×2 days, 50 mg×2 days, 100 mg×3 days

Drug dose/route of administration

1

Number of patients

Bush GH. 1962[3]

Author/Year

Present

Present

Unknown

Present

Present Probable Present

Present

Present

Unknown

Renal disease

Methyl‑prednisolone, hydromorphone

a: Absent b: Present

Absent

5 patients (vancomycin, Present capreomycin, ethambutol, isoniazid, kanamycin, streptomycin) None Present (4/6 patients) None Present None Unknown

None

Streptomycin, neomycin, bacitracin (pre‑ and post‑operative) None

Meperidine promethazine

Neomycin sinus irrigation None None

Bacitracin

None

Neomycin, Bacitracin

Other neurotoxic antibiotics

a: Unknown a: Amikacin b: 1 day b: None

3 days

48 hours 7 days

Unknown

10 hours ‑62 hours

4 hours

6 hours

7 hours

12 hours

Several hours Couple of hours 5 hours 11 days 18 hours

2 hours

Apnea duration

Table 1: Reported cases of respiratory paralysis associated with polymyxin/colistin use since 1960 to present

a: None b: None

None

None Myasthenia gravis

None

Unknown

meprobamate, prochlorperazine codeine pentobarbital Postoperative state

Meperidine, promethazine Postoperative state

None Unknown None

Postoperative state

Lumbar myelo‑meningocele Postoperative state

Other factors possibly related to apnea

Shrestha, et al.: Intravenous colistin‑induced acute respiratory failure

International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 3 | Jul-Sep 2014

Shrestha, et al.: Intravenous colistin‑induced acute respiratory failure

A total of 32 cases of colistin/polymyxin‑induced respiratory failure were found in the literature.[3‑18] All but three of those were reported before 1970s.[17,18] Recent studies have depicted the toxicities associated with colistin use to be less frequent than previously described. More purified formulations, close monitoring and better dosage might explain this finding. The most important risk factor known to be associated with respiratory failure with polymyxin use is the renal disease, which was present in 24 out of 29 patients reported. Patients with preexisting renal insufficiency had a greater likelihood of developing nephrotoxicity during colistin therapy, compared to patients with normal baseline renal function.[14] Concomitant drug therapies also play a major role in potentiating the effect of neuromuscular blockade, which was noted in 11 out of 29 patients. This includes use of other neurotoxic drugs (anesthetics, aminoglycosides, and paralytics), corticosteroids, narcotics and/or muscle relaxants. Most of the cases had other neuromuscular symptoms like circumoral tingling, paresthesias, and restlessness prior to the development of respiratory failure. The duration of apnea lasted from few hours up to several days, maximum noted to be 11 days and 20 out of 29 patients recovered, indicating reversibility of the blockade. The number of doses prior to the respiratory failure seems to be variable and range from a single dose to 45 doses [Table 1]. The management of patient with respiratory failure induced by colistin involves discontinuation of the drug and respiratory support. Intermittent monitoring of unassisted tidal volumes and forced vital capacity using a bedside spirometer will help determine recovery. Monitoring arterial blood gas helps determine the adequacy of ventilation during the period of ventilator support.[16] More importantly, one should be alert for the possibility of respiratory paralysis in any patients receiving this antibiotic and particularly in those patients with renal abnormality and with concomitant neurotoxic drug use. Careful observation, regular neurological monitoring, and early appreciation of the symptoms of neuromuscular toxicity especially of dyspnea and restlessness may prevent respiratory arrest. Neostigmine is not indicated in polymyxin or colistin‑induced neurotoxicity and may be contraindicated as seen in earlier experiments that the blocking action of polymyxin B was shown to be neostigmine resistant.[19] Intravenous calcium was reported to clinically reverse the respiratory paralysis associated with colistin. Thus, early administration of calcium gluconate IV may be helpful. Animal studies have noted the ability of polymyxin B to discharge histamine from tissue mast cells, which lead to deposition of chelated calcium along the nerve sheaths,

leading to toxicity. Swinefor thus suggested the toxicity may be prevented with prior use of antihistamines.[20] Higginbotham also reported use of heparin prevents death from respiratory arrest in mice receiving colistin.[21] The use of antihistamines and heparin in polymyxin induced respiratory failure has not been studied in human subjects.

CONCLUSION As the use of colistin increased in recent years for treatment of life‑threatening MDR infections, there are more reports of associated toxicities. Respiratory paralysis is the most serious side effect. Clinicians should be aware of colistin‑related adverse reactions, especially nephrotoxicity and neurotoxicity. Since the formulation of the drug itself has changed, it has necessitated new data with the new formulation. Regular monitoring of renal function as well as development of a tool to monitor neurological toxicity is essential to prevent and manage the toxicities associated with colistin use.

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

15. 16. 17. 18.

Falagas  ME, Kasiakou  SK. Colistin: The revival of polymyxins for the management of multidrug‑resistant gram‑negative bacterial infections. Clin Infect Dis 2005;40:1333‑41. Nation  RL, Li  J. Colistin in the 21st  century. Curr Opin Infect Dis 2009;22:535‑43. Bush GH. Antibiotic Paralysis. BMJ 1962;5311:1062. Fekety FR Jr, Norman  PS, Cluff  LE. The treatment of gram‑negative bacillary infections with colistin. The toxicity and efficacy of large doses in forty‑eight patients. Ann Intern Med 1962;57:214‑29. Small GA. Report of a case. Respiratory paralysis after a large dose of intraperitoneal polymyxin B and bacitracin. Anesth Analg 1964;43:137‑9. Perkins  RL. Apnea with intramuscular colistin therapy. JAMA 1964;190:421‑4. Rapin  M, Bagros  P, Amiel  C, Barois  A, Goulon  M. Acute interstitial nephropathy and neurologic disorders during a massive and prolonged treatment with colistin methaesulfonate. Presse Med 1965;73:1529‑34. Parisi  AF, Kaplan  MH. Apnea during treatment with sodium colistimethate. JAMA 1965;194:298‑9. Anthony MA, Louis DL. Apnea due to intramuscular colistin therapy. Report of a case. Ohio State Med J 1966;62:336‑8. Barlow MB, Groesbeek A. Apparent potentiation of neuromuscular block by antibiotics. S Afr Med J 1966;40:135‑6. Pohlmann  G. Respiratory arrest associated with intravenous administration of polymyxin B sulfate. JAMA 1966;196:181‑3. Zauder HL, Barton N, Bennett EJ, Lore J. Colistimethate as a cause of postoperative apnoea. Can Anaesth Soc 1966;13:607‑10. Lindesmith LA, Baines RD Jr, Bigelow DB, Petty TL. Reversible respiratory paralysis associated with polymyxin therapy. Ann Intern Med 1968;68:318‑27. Koch‑Weser  J, Sidel  VW, Federman  EB, Kanarek  P, Finer  DC, Eaton AE. Adverse effects of sodium colistimethate. Manifestations and specific reaction rates during 317 courses of therapy. Ann Intern Med 1970;72:857‑68. Colvard MC Jr. Respiratory paralysis secondary to the use of polymyxin B. South Med J 1971;64:652. Decker DA, Fincham RW. Respiratory arrest in myasthenia gravis with colistimethate therapy. Arch Neurol 1971;25:141‑4. Wahby  K, Chopra  T, Chandrasekar  P. Intravenous and inhalational colistin‑induced respiratory failure. Clin Infect Dis 2010;50:e38‑40. Wunsch H, Moitra VK, Patel M, Dzierba AL. Polymyxin use associated with respiratory arrest. Chest 2012;141:515‑7.

International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 3 | Jul-Sep 2014

269

Shrestha, et al.: Intravenous colistin‑induced acute respiratory failure 19. Kubikowski  P, Szreniawski  Z. The mechanism of the neuromuscular blockade by antibiotics. Arch Int Pharmacodyn Ther 1963;146:549‑60. 20. Swinefor O. Respiratory arrest and polymyxin B. JAMA 1966;196:1097. 21. Higginbotham RD. Effect of heparin on neomycin. Tex Rep Biol Med 1960;18:408‑17.

270

Cite this article as: Shrestha A, Soriano SM, Song M, Chihara S. Intravenous colistin-induced acute respiratory failure: A case report and a review of literature. Int J Crit Illn Inj Sci 2014;4:266-70. Source of Support: Nil, Conflict of Interest: None declared.

International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 3 | Jul-Sep 2014

Copyright of International Journal of Critical Illness & Injury Science is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.

Intravenous colistin-induced acute respiratory failure: A case report and a review of literature.

The emergence of multi-drug-resistant gram negative bacillary infections has regained popularity of ancient drugs such as polymyxins. We report a case...
494KB Sizes 0 Downloads 6 Views