More than 2 billion of the world’s population reside in low- and middle-income countries. In these countries, provision of emergency, essential surgical care, and anesthesia that have been shown to decrease mortality and disability is limited.1,2 One of the reasons could be that providing anesthesia in these countries can be challenging because of inadequate infrastructure and equipment. In addition, these countries have a shortage of trained anesthesiologists, and thus, nonphysician anesthesia providers generally provide anesthesia services in the rural and underserved hospitals.3–5 In such circumstances, it is necessary to use anesthetic drugs and techniques with safe profiles.
Ketamine in Low- and Middle-Income Countries
Ketamine is a potent dissociative anesthetic and analgesic with a 50-year history of clinical utility.6–8 It provides analgesia, amnesia, immobility, and loss of consciousness. It has a wide margin of safety when compared with other general anesthetics. Its sympathomimetic effects provide hemodynamic stability, which is of particular benefit in hemodynamically unstable and critically ill patients.9,10 In addition, it has bronchodilatory properties, which contribute to its safety in patients with acute pulmonary disease. Also, during ketamine anesthesia, pharyngeal and laryngeal reflexes, as well as ventilation, are generally preserved. Ketamine stimulates respiration and maintains airway patency during sedation and anesthesia over a wide dose range.11 Low-dose ketamine has been shown to antagonize opioid-induced hypoventilation in healthy volunteers.12 Ketamine can be used for coinduction with other anesthetics, thereby enhancing their synergistic action and providing cardiopulmonary stability.13,14 In addition, ketamine has been shown to be superior to fentanyl with respect to hemodynamic stability and adverse effects.15 Ketamine also minimizes the decrease in core temperature usually associated with anesthesia because it reduces the magnitude of redistribution hypothermia.16
Overall, ketamine is suitable in many clinical situations because of its safety profile (i.e., wide therapeutic range, as well as preservation of airway reflexes, ventilation, and hemodynamic stability) and suitability for administration via multiple routes (e.g., IV, IM, and intraosseous).17 It is inexpensive and easily available, and unlike modern anesthetic techniques such as inhaled anesthesia, it requires minimal equipment and training. Therefore, in many low- and middle-income countries, ketamine is the sole anesthetic.
Ketamine has been shown to be safe and effective for a wide range of surgical procedures, including short painful, long complex, and day-case procedures.18–20 Ketamine is used in all age groups, including neonates, infants, and children. In most peripheral hospitals in the low- and middle-income countries, ketamine remains the commonly used premedicant and anesthetic for pediatric patients undergoing a variety of surgical procedures.21–23 A systematic review of published literature found that caudally administered ketamine, in addition to a local anesthetic, provided prolonged postoperative analgesia with few adverse effects compared with local anesthetics alone.24 Médecins Sans Frontières, in its projects covering >50 countries around the world, uses ketamine as a component of multimodal analgesia, which includes tramadol and diclofenac, with good results.25
Although not all countries have the same levels of reliance on ketamine as an anesthetic, in resource-poor environments and in crisis, there is no substitute that is either as effective or as safe. Thus, even the rich countries that currently are not dependent on ketamine may require it in a crisis (i.e., disaster medicine and prehospital analgesic/anesthetic).
The unique properties of ketamine make it appealing for prehospital analgesia and anesthesia (e.g., surgical procedures for acute life-threatening situations such as managing major hemorrhage and traumatic amputations and to facilitate patient extrication), as well as in disaster and limited resource situations. Similarly, ketamine has an established role for challenging situations in the emergency department, including procedural sedation, difficult airway, reactive airway disease, and the uncooperative patient, as well as for fracture management and burn analgesia.26,27 Ketamine lends itself to creative and innovative modes of administration. For example, 5 mg/kg oral ketamine sweetened with soda has been used for the reduction of fractures.28 The authors concluded that ketamine in soda appears to be palatable with a rapid onset of action and few side effects, while being an inexpensive and accessible option for effective analgesia for minor procedures in the emergency room.28
Ketamine Abuse and Scheduling
Unfortunately, ketamine is used recreationally, as a “party drug.”29 There are a number of harms stemming from the chronic, recreational use of ketamine.30,31 There is also concern that some individuals develop dependence, although the incidence of this is currently difficult to gauge. Long-term physical risks of using ketamine include ulcerative cystitis and loss of bladder control. Many daily users report having tried but failed to stop using ketamine. Although a specific withdrawal syndrome has not yet been identified, tolerance to the drug develops rapidly.
In 2014, China recommended that ketamine be included as a Schedule I drug, probably because it has the most illegal ketamine users in the world.31 Of note, Schedule I medications are considered to have limited or no medical applications and, therefore, are prohibited internationally. Thus, health care providers do not have access to these drugs. If ketamine is placed on the Schedule I list, it will not be available in the low- and middle-income countries, resulting in dire consequences. Therefore, after critical consideration, the World Health Organization’s Expert Committee on Drug Dependency concluded that the public health risks from recreational use of ketamine are significantly lower compared with its medical benefits, particularly in low- and middle-income countries and in crisis situations and recommended that it should not be included as a Schedule I drug.31 On the basis of the assessments of the World Health Organization and the comments from several governments and global professional organizations, the United Nations Commission on Narcotic Drugs decided not to schedule ketamine.32 Although for now the Commission on Narcotic Drugs has decided not to schedule ketamine, this issue may reappear. Thus, it is necessary to remain vigilant in case of future attempts to schedule ketamine.
We must face the brutal fact that many hospitals in developing countries do not have anesthesia machines and the ability to provide inhaled anesthesia. There are limited numbers of trained anesthesiologists, and nonphysician anesthetists provide most anesthesia services. Many anesthesia providers have only seen tracheal tubes and supralaryngeal devices in pictures or in textbooks. Those providers who have airway accessories will likely keep them as souvenirs until they exceed the expiration dates because there are no means of getting a replacement. In many rural hospitals, patients undergo surgical procedures on room air or the delivery of oxygen from the oxygen concentrator. Providers keep the patients’ airway open by positioning and jaw-lift, whereas they use manually operated suction machines for oropharyngeal suctioning and a precordial stethoscope to monitor breath sounds, heart rate, and volume. In such situations, ketamine is a lifesaver.
Ketamine has been recognized as an anesthetic/analgesic of choice in areas with limited resources. Compared with inhaled anesthetics, which require costly equipment and appropriately trained specialists, ketamine is inexpensive and safe to administer. The anesthesia providers understand that they must use atropine to reduce the secretions, whereas the hallucinatory effects of ketamine are reduced by administering a benzodiazepine, and in most cases, diazepam is easily available. Thus, ketamine in combination with atropine and diazepam has been a reliable regimen for the anesthesia provider in low- and middle-income countries. With this regimen, the surgeon can perform varied types of surgical procedures in several settings including surgical outreach commonly performed in rural areas using makeshift operating rooms.
Let us imagine surgery in low- and middle-income countries without the only current option, ketamine. Scheduling ketamine would restrict essential surgery for populations in the world that have no other alternatives because surgeons will be constrained and surgical procedures will be limited to those that can be performed under local/regional anesthesia with or without sedation.33 Major necessary surgery will not be performed, which will lead to increased morbidity and mortality. In addition, many patients will refuse surgery because it would result in suffering that was required of patients in the era before anesthesia. This will further deepen the already acute crisis of global surgery.
Name: Girish P. Joshi, MBBS, MD, FFARCSI.
Contributions: This author involved in the conception, drafting, and revising the manuscript.
Attestation: Girish P. Joshi approved the final manuscript.
Name: Bisola Onajin-Obembe, MBBS, FWACS, MBA.
Contributions: This author involved in the drafting and revising the manuscript.
Attestation: Bisola Onajin-Obembe approved the final manuscript.
This manuscript was handled by: Hugo Van Aken, PhD, FRCA, FANZCA.
1. Walker IA, Shafer SL. The World Federation of Societies of Anaesthesiologists, International Anesthesia Research Society, and Anesthesia & Analgesia: a shared global vision. Anesth Analg. 2015;120:721–4
2. Walker IA, Bashford T, Fitzgerald JE, Wilson IH. Improving anesthesia safety in low-income regions of the world. Curr Anesthesiol Rep. 2014;4:90–9
3. Newton M, Bird P. Impact of parallel anesthesia and surgical provider training in sub-Saharan Africa: a model for a resource-poor setting. World J Surg. 2010;34:445–52
4. Holmer H, Lantz A, Kunjumen T, Finlayson S, Hoyler M, Siyam A, Montenegro H, Kelley ET, Campbell J, Cherian MN, Hagander L. Global distribution of surgeons, anaesthesiologists, and obstetricians. Lancet Glob Health. 2015;3(Suppl 2):S9–11
5. Lokossou T, Zoumenou E, Secka G, Bang’na FO, Le Polain de Waroux B, Veyckemans F, Baele P, Chobli M. Anesthesia in French-speaking Sub-Saharan Africa: an overview. Acta Anaesthesiol Belg. 2007;58:197–209
6. Domino EF. Taming the ketamine tiger. 1965. Anesthesiology. 2010;113:678–84
7. Marland S, Ellerton J, Andolfatto G, Strapazzon G, Thomassen O, Brandner B, Weatherall A, Paal P. Ketamine: use in anesthesia. CNS Neurosci Ther. 2013;19:381–9
8. Aroni F, Iacovidou N, Dontas I, Pourzitaki C, Xanthos T. Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug. J Clin Pharmacol. 2009;49:957–64
9. Morris C, Perris A, Klein J, Mahoney P. Anaesthesia in haemodynamically compromised emergency patients: does ketamine represent the best choice of induction agent? Anaesthesia. 2009;64:532–9
10. Ostermann ME, Keenan SP, Seiferling RA, Sibbald WJ. Sedation in the intensive care unit: a systematic review. JAMA. 2000;283:1451–9
11. Eikermann M, Grosse-Sundrup M, Zaremba S, Henry ME, Bittner EA, Hoffmann U, Chamberlin NL. Ketamine activates breathing and abolishes the coupling between loss of consciousness and upper airway dilator muscle dysfunction. Anesthesiology. 2012;116:35–46
12. Persson J, Scheinin H, Hellström G, Björkman S, Götharson E, Gustafsson LL. Ketamine antagonises alfentanil-induced hypoventilation in healthy male volunteers. Acta Anaesthesiol Scand. 1999;43:744–52
13. Abbasivash R, Aghdashi MM, Sinaei B, Kheradmand F. The effects of propofol-midazolam-ketamine co-induction on hemodynamic changes and catecholamine response. J Clin Anesth. 2014;26:628–33
14. Butt MN, Ahmed A. The Induction dose of propofol with ketamine-propofol and midazolam-propofol co-induction. J Anesth Clin Res. 2013;4:371
15. Goyal R, Singh M, Sharma J. Comparison of ketamine with fentanyl as co-induction in propofol anesthesia for short surgical procedures. Int J Crit Illn Inj Sci. 2012;2:17–20
16. Ikeda T, Kazama T, Sessler DI, Toriyama S, Niwa K, Shimada C, Sato S. Induction of anesthesia with ketamine reduces the magnitude of redistribution hypothermia. Anesth Analg. 2001;93:934–8
17. Olaussen A, Williams B. Intraosseous access in the prehospital setting: literature review. Prehosp Disaster Med. 2012;27:468–72
18. Ikechebelu JI, Udigwe GO, Obi RA, Joe-Ikechebelu NN, Okoye IC. The use of simple ketamine anaesthesia for day-case diagnostic laparoscopy. J Obstet Gynaecol. 2003;23:650–2
19. Olasinde AA, Oluwadiya KS. Anesthesia practice in a hospital, developing countries: an 18 month’s experience. Intl J Third World Med. 2005;3:1–4
20. Elusoji SO, Iribhogbe PE, Osime OC. Thyroidectomy under ketamine anaesthesia in a semi urban hospital in Nigeria. Pak J Med Sci. 2009;25:695–7
21. Ouro-Bang’na Maman AF, Kabore RA, Zoumenou E, Gnassingbé K, Chobli M. Anesthesia for children in Sub-Saharan Africa—a description of settings, common presenting conditions, techniques and outcomes. Paediatr Anaesth. 2009;19:5–11
22. Mahmoud AO, Ayanniyi AA, Oyedepo OO. Pediatric ophthalmic indications for examination under anesthesia in Ilorin, Nigeria. Ann Afr Med. 2010;9:181–3
23. Alagbe-Briggs OT, Onajin-Obembe BO. Experience with ambulatory anaesthesia for paediatric inguinoscrotal surgery in a surgical outreach. J Med Med Sci. 2013;4:225–9
24. Schnabel A, Poepping DM, Kranke P, Zahn PK, Pogatzki-Zahn EM. Efficacy and adverse effects of ketamine as an additive for paediatric caudal anaesthesia: a quantitative systematic review of randomized controlled trials. Br J Anaesth. 2011;107:601–11
25. King C. Postoperative analgesia in rebel territory in Cote d’Ivoire. Anaesthesia. 2005;60:419–20
26. Jamora C, Iravani M. Unique clinical situations in pediatric patients where ketamine may be the anesthetic agent of choice. Am J Ther. 2010;17:511–5
27. Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 2011;57:449–61
28. Ogboli-Nwasor E, Amaefule KE, Audu SS. Use of oral ketamine for analgesia during reduction/manipulation of fracture/dislocation in the emergency room: an initial experience in a low-resource setting. Pain Studies Treatment. 2014;2:17–20
29. Ng SH, Tse ML, Ng HW, Lau FL. Emergency department presentation of ketamine abusers in Hong Kong: a review of 233 cases. Hong Kong Med J. 2010;16:6–11
30. Morgan CJ, Curran HVIndependent Scientific Committee on Drugs. . Ketamine use: a review. Addiction. 2012;107:27–38
33. Gawande A. Two hundred years of surgery. N Engl J Med. 2012;366:1716–23