Ketamine and Low-Resource Countries

Abstract

Safe anaesthesia and surgery are piloted to reduce the morbidity and mortality associated with anaesthesia and surgery, and improve surgical outcomes. This goal is far-fetched in developing countries as a result of limited manpower, poor operation theatre infrastructure, unavailability of equipment, life-saving drugs, and anaesthetic agents. Postoperative pain is also widely undertreated in this environment, mostly due to financial constraints patients and their relatives face and the unavailability of analgesics. Sometimes the physicians face problems associated with their resource-limited working environment, such as unreliable electricity, unavailability of compressed oxygen and other gases, sophisticated machines, and modern drugs. Thus, easy adaptability and proper utilisation of available resources have been described as a resounding quality required of anaesthetists working in developing countries, to thrive and provide anaesthetic services. Ketamine is readily available in resource-limited environments, and adaptability to the use of this drug has made it possible for the anaesthetist to provide anaesthesia, pain care services, sedation, and save lives.

1. Introduction

Anaesthesia practice remains a challenge in the developing and low-resource or income countries of the world, particularly in Sub-Saharan Africa where the growing population and the need for surgical and anaesthesia intervention are overwhelming the insufficient number of trained anaesthesia personnel and available resources [1]. This has been described by some clinicians as problems associated with human, technical, investment, and educational resources [1, 2]. Anaesthesia service delivery has also been negatively affected by poor operation theatre infrastructure, unavailability of equipment, lifesaving drugs, and anaesthetic agents, inadequate clean water supply, transportation, electricity, oxygen, and blood banks services [2]. Thus, easy adaptability and proper utilisation of the available resource remains the keyway to delivering safe anaesthesia services in the low-resource countries. The regular use of a cheap, safe, and accessible drug called “ketamine” in clinical practice in the resource-limited countries has become overwhelming, as a result of the unavailability of anaesthesia equipment, oxygen, lifesaving drugs, and anaesthetic agents. A drug that is frequently described as a “unique drug” because it shows hypnotic, analgesic, and anterograde amnesic effects [3].

Ketamine is used in the operating room during induction and maintenance of hypnosis, with its analgesic property being beneficial for intraoperative and early postoperative analgesia. Its place in procedural sedation and total intravenous anaesthesia is insurmountable. Ketamine is used as an adjuvant together with other drugs during peripheral nerve blocks and neuraxial blocks to prolong the duration of analgesia provided by these techniques of anaesthesia [3].

Developing countries and low-income/resource countries are often used interchangeably. A developing country is a nation with a less developed industrial base and a low Human Development Index (HDI) relative to other countries. The term low-income country is often used to refer only to the economy of the country. The World Bank classifies the world’s economies into four groups, based on Gross National Income (GNI) per capita, and these are high, upper-middle, lower-middle, and low-incomes countries. Low-income countries have a GNI per capita of less than 1026 United State dollars [4, 5]. More than 2 billion of the world’s population reside in low- and middle-income countries. In most of these areas, the healthcare systems suffer from issues that involve institutional, human resources, financial, technical, and political developments. The provision of emergency, essential surgical care, and anaesthesia are quite limited. This area of the world has not been able to meet up with the World Health Organization (WHO) 2007 proposed framework of healthcare systems. World Health Organization proposed that, for a country to have an effective healthcare structure, components, such as service delivery, healthcare workforce, healthcare information systems, medicines and technologies, financing, and leadership/governance must be met. Poor governance, funding, and human resource challenges are linked to ineffective integration of services in resource-limited nations [6].

The clinical role of ketamine in providing anaesthesia in low-income countries with inadequate healthcare infrastructure and equipment has been demonstrated. Despite health care being identified as a strategic priority, relatively little information has been established about the capacity of the health system in low-income countries to deliver essential and safe surgical and anaesthesia services. In many rural hospitals in developing countries, patients undergo surgical procedures on room air or rarely with the delivery of oxygen from the oxygen concentrator. The anaesthesia providers keep the patients’ airway open by simply positioning, chin lift, and jaw thrust. The airway is suctioned by the use of mucus extractors, rubber bulb suction devices, and rarely with foot-pedal manually operated suction machines as a result of lack of electricity. An improvised precordial stethoscope becomes vital in monitoring a patient’s breath sounds, heart rate, and volume. Many of these hospitals do not have anaesthesia machines and the ability to provide inhaled anaesthesia, thus, in such situations, ketamine becomes a lifesaver [3, 7, 8].

2. Anaesthesia practice in low-resource countries

In the years 2000 and 2007, Hodges and co-workers described the state of anaesthesia delivery in low-resource and Sub-Saharan African countries as inadequate, with emphasis that in the twenty-first century, millions of people in this area of the world may not have access to safe anaesthesia and pain relief during surgery and childbirth, which are considered as a basic human right. This is not different from another report by Adamu and co-workers in 2010, which noted the increasing difficulty with the preparation of patients for emergency surgery and getting them to surgical theatre within an acceptable time in limited-resource countries. The delays were related to the constraints in poor health institutional organisation and the socio-economic status of the patients. Thus, a significant portion of the patients waits too long for emergency surgery at the expense of perioperative morbidity and mortality [1, 9, 10].

An estimation of 234 million surgeries is performed every year to alleviate some disabilities and reduce the risk of death from some common medical conditions, and this is achieved with the help of anaesthesia. However, access to safe surgery has been suggested to be 3.5% in the world third poorest countries. An epidemiological study reported that 30% of the world’s population lack access to safe surgery, as well as safe anaesthesia. In most areas of Sub-Saharan Africa, government hospitals provide few supplies for resuscitation, anaesthesia, and surgery, making patients pay out of their pockets or provide materials for their surgical and anaesthesia care. Sometimes, delays in the procurement of these resources and materials often lead to delayed surgical and anaesthesia intervention, with the poor perioperative outcome. Ketamine has been shown to be safe and effective for a wide range of surgical procedures and its suitable in many clinical situations because of its safety profile [8, 11, 12].

The quality and type of anaesthesia services provided during surgery are highly related to perioperative outcomes. Nevertheless, this can be affected by the level of training of the medical personnel, the availability of surgical theatre infrastructure and resources, anaesthesia drugs, unreliable electricity, unavailability of compressed oxygen and other gases, anaesthesia machines, and modern drugs—a problem common with low-income countries. Thus, physician anaesthetists in this environment have learned to adapt and utilise any available resources to provide safe anaesthetic services and save lives. The use of ketamine as the sole anaesthetic agent has been in clinical use for a long period of time and it has been found to be beneficial and cost-effective. Ketamine has a place in the management of acute pain through intraoperative low-dose infusion, even in opioid-tolerant patients. It has likewise been used in low-resource countries after surgery with minimal psycho-mimetic effects [3, 8].

3. Ketamine anaesthesia in low-resource countries

Ketamine has gained lots of credit in surgical practice in low-resource countries. It has also been demonstrated to be vital in global healthcare practice too. Limited resource countries rely heavily on ketamine as a sole anaesthetic agent in the face of the growing need for surgical services. The global burden of diseases preventable by surgery is on the rise and is expected to surpass those of human immunodeficiency virus, tuberculosis, and malaria by 2026. Ketamine has been shown to be the most widely used and safest anaesthetic drug, as reflected by being ‘always available’ according to 92% of anaesthetists surveyed in Uganda [1, 13].

The clinical administration of ketamine has been shown to be very effective in a wide range of surgical procedures, even amongst all age groups. Ketamine can be administered conveniently through different routes. The intravenous route offers the optimal channel of administration, but sometimes it’s difficult to achieve in emergencies, children, and obese patients. Ketamine can be administered efficiently through the intraosseous and intramuscular routes. The intramuscular administration of ketamine during anaesthesia, is associated with a longer recovery time. The oral administration of ketamine has also been documented, even with its mixture with soda to enhance the oral administration, however, this route has a reduced bioavailability [14, 15, 16].

Ketamine anaesthesia provides analgesia, amnesia, immobility, and loss of consciousness. It has been found to have a wide margin of safety when compared with other general anaesthetic agents. In addition, its sympathomimetic effects provide hemodynamic stability, which is beneficial in critically ill and hemodynamically unstable patients. Furthermore, the use of ketamine in pain medicine (multimodal analgesia, chronic pain, and palliative care), critical care (status epilepticus), emergency medicine, and psychiatry (depression) in developing countries with a shortage of trained personnel could not be overemphasised [3, 7, 8]. Nevertheless, the administration of ketamine is associated with some side effects. It causes dissociative anaesthesia, which alters the sensory perceptions of the patients. It can increase the incidence of postoperative nausea and vomiting, cause transient apnoea especially when administered rapidly, and increases salivary secretions, which may increase the incidence of laryngospasm. The increased salivation can be minimised by co-administration of atropine. Ketamine has been found to provoke imaginative, dissociative states and psychotic symptoms due to its NMDA-antagonistic action, as well as severely impair semantic and episodic memory. It can also cause various emergent phenomena when the patient is awakening from anaesthesia. This has been described as a floating sensation, vivid pleasant dreams, nightmares, hallucinations, and delirium [17, 18].

Most clinicians and nurses involved in anaesthesia service providers understand that they must add benzodiazepines, such as diazepam or midazolam, to combat the hallucinatory effects of ketamine and the emergence phenomenon. Nevertheless, diazepam is readily available and cheap in low-resource countries, thus, ketamine in combination with atropine and diazepam forms a reliable regimen for the conduct of total intravenous general anaesthesia for different modalities of surgery, with room air and minimal equipment [1, 17].

The use of intravenous ketamine at the induction dose of 2 mg/kg in adults or 1 mg/kg in children, followed by an increment of 1–1.5 mg/kg for maintenance of the anaesthesia. While the patients were pre-medicated with intravenous atropine 0.6 mg in adults and 0.3 mg in children plus diazepam 10 mg in adults and 0.45 mg/kg in children was documented in a study conducted in Nigeria, that had the incidence of general anaesthesia with intravenous ketamine of 58.4%. This study involved different varieties of surgeries, such as intra-abdominal operations (herniorrhaphies and herniotomies), perineal, pelvic, and genital surgeries, as well as extremities, chest, head, and neck surgeries. A retrospective study reviewed 295 cases of laparoscopy that were performed over the period of 28 months at a fertility healthcare facility in Nigeria that does not have an anaesthesia machine or trained anaesthesia personnel. They showed that the regimen of atropine-ketamine-diazepam general anaesthesia was safely used for all the patients that had day-case laparoscopy. Elusoji and colleagues also reported the safety of using ketamine anaesthesia in combination with diazepam in 55 patients that had a thyroidectomy in a low-resource country. They reported complications, such as hallucination and postoperative restlessness, which were managed with intravenous diazepam, chlorpromazine, or paraldehyde (Table 1) [19, 20, 21].

Author	Objective	Country	Variables	Discussion	Conclusion
Hodges et al. [1]	Assessment of anaesthesia facilities in different units.	Uganda	Availability of ketamine	Ketamine is always available in 92% of the period	Identification of shortages of personnel, drugs, equipment, and anaesthesia training in Uganda
Vo et al. [13]	Use of ketamine as an anaesthetic compared with basic anaesthetic infrastructure and equipment at facilities in 22 low- and middle-income countries.	Low- and middle-income countries	Ketamine anaesthesia	Current ketamine use exceeds the availability of other anaesthetic options.	Restrictions on ketamine need to consider the larger impact on the global burden of surgical diseases where ketamine is vital in the care of surgical patients.
Olasinde et al. [19]	To highlight the experience from a specialist hospital in south-western Nigeria	Nigeria (South-West)	Ketamine anaesthesia	52% ketamine utilisation	Ketamine and local infiltration with lidocaine are commonly used in this environment.
Ikechebelu et al. [20]	A retrospective review of 295 cases of laparoscopy over 28 months in a fertility unit.	Nigeria (South-East)	Ketamine is used by an untrained healthcare personnel	Ketamine uses for laparoscopic procedures	Ketamine produces a safe, effective and simple general anaesthesia and is recommended for use in day-case laparoscopy
Elusoji et al. [21]	To evaluate the efficacy and safety of ketamine hydrochloride anaesthesia without endotracheal intubation in thyroidectomy.	Nigeria	Ketamine anaesthesia	Ketamine uses for thyroidectomy	Ketamine anaesthesia is safe and economical for thyroidectomy.
Lonnée et al. [22]	To assess the type of anaesthesia used for caesarean delivery, the level of training of anaesthesia providers, and to document the availability of essential aesthetic drugs and equipment.	Zimbabwe	Rural setting	100% ketamine utilisation. Shortage of essential drugs for anaesthesia, inconsistent use of recovery area, and insufficient blood supplies.	Training of medical officers and nurse anaesthetists should be strengthened in leadership, teamwork, and management of complications.
Nuhu et al. [23]	Evaluation of workforce situation and availability of anaesthetic drugs/equipment in public secondary health facilities.	Nigeria (North-Central)	Ketamine anaesthesia	100% utilisation	There is a dearth of aesthetic and surgical workforce and basic infrastructure in public hospitals.
Masaki et al. [24]	To assess the feasibility and safety of ketamine in support of obstetric and gynaecologic surgeries in severely resource-scarce settings when there is no available anaesthetist.	Kenya	Ketamine anaesthesia	Improved provider’s competency due to ketamine raining	Ketamine is safe for use in support of emergency and essential obstetric and gynaecologic surgeries in extremely resource-limited settings when no anaesthetist is available.
Makin et al. [25]	To gain surgeons’ perceptions on performing operations supported by ketamine and to recommend best practices and techniques.	Low-income countries.	Ketamine is used amongst surgeons	Global standards on ketamine training and use should be established.	Ketamine is safe, can provide increased access to emergency and essential surgery, and requires few operative technical changes.
Koka et al. [26]	To describe the anaesthesia practice at two tertiary hospitals	Sierra Leone	Ketamine anaesthesia	Utilisation rate of 44.7%	Gaps in the application of internationally recommended anaesthesia practices at both hospitals are caused by a lack of resources.

Table 1.

Summary of ketamine in low-resource countries.

4. Anaesthesia service adaptations

4.1 Anaesthesia providers

Anaesthesia is an essential part of healthcare services. In developed countries and some of developing countries, anaesthesia is not merely limited to the operating room, but the services also involve the emergency room, intensive care unit, angiography-catheterisation laboratory, magnetic resonance imaging suite, pain clinics, resuscitative rooms, electroconvulsive therapy room, and other life-saving hospital services. These services require the skill of trained anaesthesia providers, however, in most low-resource countries, there are still no strategic measures for assessing the safe anaesthesia services, particularly in rural areas because of the shortage of anaesthesia personnel. In most of these areas, the health care system is usually overburdened by patients load with limited or no anaesthesia provider.

The number of physician anaesthetists in most low-resource countries is below what is needed to provide a safe and quality anaesthesia service. A study conducted by Davies and co-workers recommended a minimum of four physician anaesthetists per 100,000 population for the provision of reasonable, safe, and standard anaesthesia care for surgical interventions. However, this figure is far-fetched in developing countries with steaming and growing populations [27]. World Federation Societies of Anaesthesiologists (WFSA) workforce survey that was based on the 2015 world population estimated that to achieve a minimum density of 1 per 100,000 physician anaesthetists in all countries, over 8000 additional physician anaesthetists would be required. While over 136,000 additional physician anaesthetists would be required worldwide to achieve 5 per 100,000. Nevertheless, the majority of the countries in Sub-Saharan Africa and some in Asia have a physician anaesthetists density of <1 per 100,000 population [28].

Anaesthesia professionals, especially in Sub-Saharan Africa, are often poorly remunerated, supported and undervalued. The recruitment process of healthcare personnel often neglects the anaesthesia providers, thus resulting in shortages of anaesthesia physician and their allied personnel, such as nurse anaesthetist, anaesthesia technicians, and anaesthesia attendants. In some low-resource countries, some of the anaesthesia physician support staff are not included and are sometimes poorly placed in the civil service, making it difficult for them to be remunerated. Ho et al. reported in 2019 that 30.4% of the 344 medical facilities they surveyed had no anaesthesia provider at any level (physicians, nurses, or technicians) accessible for patient care [29]. In most low-income countries, anaesthesia services are often provided by unqualified physician personnel, nurse anaesthetists, or anaesthesia technicians who are trained by physician anaesthetists, to use anaesthesia resources to provide safe anaesthesia services. This day-to-day reality of shortage of physician anaesthetists in the operating room coupled with a lack of resources, persuades the available anaesthesia providers to use simple and effective techniques that are not too expensive and readily available.

The properties of ketamine anaesthesia, such as analgesia, amnesia, immobility, and loss of consciousness make it the technique of choice, alongside local and spinal anaesthesia in low-resource countries. In a study reported in the Democratic Republic of Congo, 771 patients had general anaesthesia with ketamine in an operating room that had no physician or nurse anaesthetist, but untrained personnel. They reported that most of their patients were females (85.86%) and 97.4% of the patients who had surgery were classified as ASA II and the intermediate surgical risk was more represented in 82.9%. The adverse event they noted were arterial hypertension (10.2%), salivation (5.5%), respiratory distress (4.8%), agitation on awakening (30.8%), and hallucinations (22.6%), respectively. They did not record any mortality. Indicating ketamine is safe and effective, even in regions where anaesthesia is conducted by untrained anaesthesia personnel [30].

Anaesthesia in Zambia, a low-resource country, is under-developed and under-resourced. The anaesthesia specialty is focused almost exclusively on intraoperative patient care. In small hospitals and hospitals in rural areas, there is lack adequate staffing. A study conducted in this country showed that 80% of anaesthesia cases were performed by non-physicians with little or no formal training in anaesthesia. The reliance of the anaesthesia providers on ketamine is a result of inadequate training, inexperience with, and access to, more advanced equipment like laryngoscope and materials like endotracheal tubes. A limited number of anaesthetists have almost no involvement in emergency medicine and pain therapy [31].

4.2 Shortage of modern drugs and anaesthesia agents

In most areas of developing countries, a shortage of essential drugs used in anaesthesia practice is a common problem. Thus, the anaesthesia providers engage in the use of simple and effective techniques that are not expensive, but readily available. The properties of ketamine make the drug a product of choice, for simplified general anaesthesia like total intravenous anaesthesia, alongside its use as an additive to prolong the analgesic effect of local and neuraxial anaesthesia. In well-equipped health institutions with trained anaesthesia personnel, inhalation anaesthesia is normally the first choice of maintaining hypnosis during anaesthesia; however, ketamine has proved to be useful in settings without recovery facilities, as well as trained anaesthesia providers and in areas where patients need to wake up in their own beds in the various wards, especially in low-income and middle-income countries, and in emergency situations [1, 32]. Ketamine anaesthesia was found to predominate other techniques or modes of anaesthesia in most hospitals evaluated (72.9%), whereas inhalational anaesthesia was only available in 56.2% of the hospitals. Also, techniques of anaesthesia like regional and spinal anaesthesia, were available in 58.9 and 65.9% of hospitals, respectively studied [28].

A study published in Uganda in 2007 stated that drugs used for the conduct of anaesthesia are usually limited in supply. The availability of narcotics is 45%, nondepolarizing muscle relaxants 15%, inhalational agents 38%, and intravenous induction agents 59% [1]. In another study done by Khan in Pakistan, he reported that there is a non-availability of some essential drugs, such as narcotics, inhalational agents, induction agents, and some vasoactive drugs in Pakistan [33].

There are several factors that contribute to the anaesthesia drug shortages, some of them are common in both high-income and low-income countries. For example, regulatory issues, manufacturing problems, raw material acquisition problems, business decisions based upon the profitability of some drugs, and disturbances or faults in the supply chain. The factors that affect low-income countries alone include issues of licensing by healthcare regulatory authorities, imports from abroad, shortage of ingredients for local manufacture, government policies, and drug smuggling to other countries. The implication of anaesthesia drug shortage is that it can result in the cancellation of surgery which may be psychologically traumatic to both patients and their families. The economic implication for both patients and hospitals are incurred from prolongation of hospital stay and higher risk of exposure to hospital-acquired infections [34, 35].

4.3 Shortage of anaesthesia vapours and compressed gases

The anaesthesia gas supply system is designed to provide a safe, cost-effective and convenient system for the delivery of medical gases at the point of use in the hospital. The medical gases used in anaesthesia and intensive care medicine are oxygen, nitrous oxide, medical air, Entonox, carbon dioxide, and heliox. Oxygen is one of the most widely used gases for life-support and respiratory therapy besides anaesthetic procedures. There is a lack of adequate supply of oxygen in most of low-resource countries. In a recent survey of anaesthetic care in 22 low- and middle-income countries, uninterrupted access to oxygen was available in only 46% of the healthcare facilities, while 35% reported no access to oxygen. Ketamine can be administered through various routes and it does not require the availability of oxygen, electricity, anaesthetic equipment, or trained anaesthesia providers, all of which remain scarce in low-resource countries. Hence, ketamine is the most widely used and safest anaesthetic drug in resource-limited environments [13].

5. Conclusion

Ketamine is an example of how an old drug can still be renowned in the practice of medicine. It has been recognised as the sole anaesthetic/analgesic of choice in areas with low resources. Ketamine administration does not require costly equipment or appropriately trained physician anaesthetists, and it is cheap, readily available, and safe, Ketamine is effective in a wide range of surgical procedures, including short painful, long complex, and day-case procedures. The use of ketamine in low-resource countries has enhanced safe anaesthesia and surgical care, thus reducing perioperative morbidity and mortality, as well as improving surgical outcomes. The regular use of this cheap, safe, and accessible drug called “ketamine” in clinical practice in resource-limited countries has become overwhelming, despite the dwindling number of trained anaesthesia providers.

Acknowledgments

I want to express my gratitude to God Almighty, for granting me the knowledge and wisdom to contribute a chapter to this book. Also, for helping me to find my ground in human capacity building in Anaesthesia.

Conflict of interest

The author declares no conflict of interest.