Dr Sher Mohammed and authors discuss the ABC Approach while managing patients experiencing Delayed Recovery from GA
Historical and Spiritual Perspectives
Almost 2000 years back, Jairus was an official from the local synagogue. He was aware about the miracles of Jesus and begged him to cure his sick daughter. While Jesus and his disciples were on the way,they received the message that the 12 years old girl had died.
When he got to the Jairus’s house, Jesus took his disciples-Peter, James and John (the inner circle) and the child’s parents into the room. Jesus heals by touch when he takes little girl by hands and says “Talitha cumi” which means “Little girl, get up”. He instructs her parents to give her something to eat(Mark 5:21-24,35-43)
Qur’an – Sura al-Imran(The Family of Imran)3:49 states, I heal him who was born blind, and the leper, and raise the dead to life-by Allah’s Will.
Today some people suggest that the little girl was not dead but was in a diabetic coma and this is why Jesus gives his instructions to feed the child.
Related Definitions
A conscious individual, as defined in the Oxford English Dictionary as ‘awake and aware of the surroundings and identity’.However, consciousness represents a continuum with varying levels of alertness.
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened ,fails to respond normally to painful stimuli, light or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions[1].
Adequate recovery from GA has been defined as ‘a state of consciousness of an individual when they awaken or become rousable and aware of surroundings and identity’[2]
The Era of ERAS
Enhanced Recovery After Surgery(ERAS) has been implemented in the UK since 2009.It refers to patient-centred, evidence-based multi-disciplinary team development pathways for a surgical speciality and facility culture to reduce patient’s stress response, optimise their physiologic function and facilitate street fitness. ERAS pathways have been shown to reduce post-operative complications and hospital stay in patients undergoing elective colorectal surgery[3].
With the use of fast acting anaesthetic agents, patient usually awaken sooner in post-operative period. But there are situations in which the patient may not recover as quickly as planned and that results in delayed discharge from Post Anaesthetic Care Unit and subsequently from the hospital.
Delayed awakening after GA and sedation is not an uncommon complication of anaesthesia. The main factors responsible for delayed emergence are categorised as patient factors, surgical factors and pharmacological factors.
This review article aims to briefly summarise risk factors that may contribute to delayed awakening from anaesthesia /sedation i.e. acronym approach “SOMNOLENCE”. It also highlights the presenting features of this type of scenario and the ABC approach while managing it.
Patient factors resulting in delayed recovery/ SOMNOLENCE after GA and Sedation
Age: Geriatric patients show increased sensitivity to general anaesthetics, opiates and sedatives due to the progressive decline in brain functioning. Evidence shows that the dose of opiates be reduced by 50% in elderly patients[4].
Gender: Gender difference in sensitivity to anaesthetics is another debated factor. Buchanan et al[5] showed that women have less sensitivity to the sedative effects of anaesthetics which results in faster recovery. Also emergence times were faster in premenstrual women than in postmenstrual ones. Other studies have shown that women have increased sensitivity to muscle relaxants whereas males seem to be more sensitive to propofol[6].Apfel Baum reported that men are 1.4 times more likely to have delayed recovery than women[7].
Metabolic factors: Hypoglycaemia is one of the most dreaded complication found in diabetic patients undergoing surgery[8].Because GA masks cognitive dysfunction and the clinical signs of hypoglycaemia such as tachycardia and diaphoresis, severe hypoglycaemia can have serious brain effects. Hypoglycaemia can provoke delayed emergence in individuals with a history of poorly controlled diabetes. Similarly prolonged starvation can induce hypoglycaemia which may result in delayed emergence from anaesthesia in non-diabetic patients[9]. Severe hyperglycaemia can cause dehydration, drowsiness, acidosis, hyperosmolality and hyperviscosity (predisposing factors to cerebral oedema and thus prolonging recovery from anaesthesia).
Patients with myxoedema and neuromuscular pathologies are likely to take long time to recover from anaesthetics. Patients with Alzheimer’s disease, subarachnoid haemorrhage, congestive heart failure, chronic renal failure and chronic liver failure will experience prolonged somnolence in the niche of peri-anaesthetic care.
Body habitus: Males with a higher percentage of fat have a tendency to delayed awakening after propofol anaesthesia, an effect that is not seen in women[10].With the exception of neuromuscular drugs, lean body weight is the optimal dosing scale for most drugs used in anaesthesia especially opioids and anaesthetic induction agents[11]. List-1 shows the patient factors which affect the emergence from GA and sedation (acronyms are used to memorise them).
List-1: Patient factors resulting in prolonged ecovery (SOMNOLENCE) after anaesthesia
Surgical procedures after which prolonged SOMNOLENCE is expected
Hypothermia reduces the metabolic rate and elimination of the drugs and enhances the effect of anaesthetics. Hypothermia also affects the affinity of haemoglobin for oxygen contributing to poor tissue oxygenation. Hypothermia during emergence from anaesthesia causes shivering and increased O2 consumption which in turn increases lactate levels. In addition, the reduced perfusion and metabolism of the drugs increases the duration of action of sedatives and muscle relaxants. The internal body temperature of <330C reduces the MAC value of volatile agents i.e. For each 10C drop in temperature, the MAC value drops by 5-7% enhancing sedation and lengthening the recovery time[12].
Certain surgical procedures are associated with prolonged recovery from anaesthetics. Sitting craniotomy(air embolism) and steep Trendelenburg postures during surgery( cause brain oedema),the use of cardiopulmonary bypass(micro-emboli),carotid end-arterectomies (carotid blow out) are likely to take longer to recover from anaesthesia.
A case has been reported in which a 73 year old with Dandy Walker Malformation (DWM) underwent CABG which was complicated by delayed awakening. DWM is a rare posterior fossa malformation defined by hypoplasia and upward rotation of cerebellar vermis. The patient remained intubated for 6 days[13].
List-2 shows the surgical procedures associated with prolonged recovery(SOMNOLENCE).
Drug factors resulting in prolonged SOMNOLENCE after GA/sedation
Based on the principles of PK, once the administration of a drug has finished, its residual effects are influenced by a series of factors related to the dose, metabolism, blood transport, distribution and excretion.
The inappropriate dose of drugs represents one of the main causes of delayed awakening from GA. An improper dosage/timing may be due to a malfunction of the equipment that deliver drugs or to a calculation error. A special issue concerns the body weight and habitus, because a relative drug overdose is common in obese patients who receive a dosage of anaesthetics based on real body weight, optimal dosage of most medications used under anaesthesia should be calculated on the lean body mass.
Different conditions can alter the metabolism and excretion of drugs and contributes to prolonged recovery e.g. liver or renal failure. In these patients, the reduced drug metabolism or clearance leads to an increased duration of action. Moreover, renal failure can impair the protein binding through alteration of the acid-base disturbances. Severe hypothyroidism can also reduce metabolism.
The drug interactions between different anaesthetic agents or between anaesthetic agents and the medications used for chronic conditions can also occur. Example of the former is midazolam and alfentanil which are both metabolised by the same P450 iso-enzyme, duration of effect is prolonged if both are co-administered. Similarly, prolonged recovery is reported after gabapentin and ketamine being used simultaneously[14].
Patients who are depressed and taking MAOIs or SSRIs may experience severe drug interactions with IV agents that can result in hyper/hypotension and postoperative coma(up to a full blown serotonergic syndrome). Other drugs that result in drug interactions include St. John’s Wort, ginseng, lithium, ondansetron, metoclopramide, codeine, fentanyl and oxycodone. Severe symptoms may include tachycardia, shock and fever. Other abnormalities include metabolic acidosis, rhabdomylsis, seizures, renal failure and disseminated intravascular coagulation (arising as a result of hyperthermia)[15].
Hypoalbuminaemia and reduced volume of distribution can lead to an increased free drug and enhancement of effect. This aspect is important in fragile and malnourished patients.
List -3: Drug factors resulting in prolonged recovery (SOMNOLENCE) after anaesthesia
Another issue is that of anaesthetic drugs and the adjuvants being used. The use of sedatives as premedication and for induction of GA will potentiate propofol effect because both classes are GABA agonists. The commonly used drug is midazolam, its effect occur in 5-10 minutes and has an elimination T1/2 of 1.5-2.5 hours(increased with subsequent doses).Geriatric patients are very sensitive, especially if opiates are co-administered which can lead to respiratory depression causing hypercapnia, hypoxia and delayed awakening. Maeda et al[16] reported that chronic use of benzodiazepines represents an independent predictor of delayed emergence.
While using propofol TIVA, less predictable variables are patient related factors. Genetic variations of the enzymes that metabolise propofol, although rare, can be a reason for prolonged somnolence. Genetic polymorphism of the main enzymes that metabolise propofol(cytochrome P450 2B6 and uridine 5-diphospho-glucuronosyl transferase 1A9) were reported in a patient who had delayed awakening from propofol (70 minutes to 3 hours) twice over 2 years, Yonekura et al[17].These two enzymes are responsible for hydroxylation and glucuronidation of propofol. Therefore, genetic variations in propofol metabolism should be addressed in patients with incomprehensible prolonged somnolence.
Opiates induce analgesia and sedation but also respiratory depression, reducing sensitivity of the brain stem chemoreceptors to CO2.This leads to hypercapnia and CO2 narcosis, although it varies from patients to patients and is influenced by co-administration of other anaesthetic agents. Respiratory depression responds quickly to opiate antagonist; however, naloxone is a short acting drug, and the patient should be carefully monitored for the possible recurrence of respiratory depression.
Residual muscle relaxant effect or inadequate reversal will lead to hypercapnia further worsening recovery from GA(in order to avoid awareness, the patient will need to be re-sedated and thus prolonging recovery from anaesthesia).Scoline apnoea is also a well-known cause in susceptible populations. Deficiency of plasma cholinesterase prolong block produced by succinylcholine, therapeutic plasma concentrations persist because of decreased metabolism. Extension of the block is variable and depends upon the genotype[18].
Clinical features of prolonged Recovery/Somnolence after GA/sedation
The problem of delayed emergence from anaesthetics is not an uncommon complication of anaesthesia and often represents a challenge for the anaesthetists who must make an accurate diagnosis and treat accordingly. The condition is mostly benign but rarely it may be due to more serious problems such as hypoxic brain injury or neurologic problem like brain haemorrhage .
Clinically, delayed emergence presents with an altered mental state featuring sedation, lack of initiative, and lack of adequate response to stimuli. It is often associated with respiratory complications, and lack of protective airway reflexes with an increased risk of aspiration. Altered conscious state can be associated with hypoventilation that in turn, can lead to hypoxia and hypercapnia.
A clinical approach is particularly helpful to identify possible causes. Since there is no dedicated tool for monitoring recovery after anaesthesia, the clinical assessment is carried out by referring to the scales commonly used for evaluating the state of consciousness. In the niche of peri-operative care, Aldrete scoring is used to assess recovery from anaesthetic and discharge from the PACU. Aldrete scoring takes into consideration Activity level(0-2),Breathing(0-2),Circulation(0-2),Conscious level(0-2) and SaO2(0-2).Maximum score is 10 and a score of at 9 is required for a patient to be discharged from PACU.
Traditionally, GCS is largely used to assess the state of altered consciousness, although used for assessing a patient with head injury, it can be used in other settings as well. Score of <8 indicates a slow awakening and >12 is suggestive of awakening.
A few screening tools are used in the niche of peri-operative care i.e. Nursing Delirium Screening Scale and Richmond Agitation-Sedation Scale. Confusion Assessment Method uses the presence of markers such as 1. Acute onset
- Inattention
- Disorganised thinking
- Altered consciousness
- Memory impairment
- Hallucinations
- Altered sleep pattern
No delirium 0-2 score
Mild delirium 3-5 score
Severe delirium 6-7 score
Richmond Agitation- Sedation Scale
New antidotes of anaesthetic interest introduced in the recent past
Antidotes are designed to change kinetics and accelerate the elimination of toxins from the body. Currently, they are used in conjunction with other techniques such as gastric lavagae, haemodialysis and haemoperfusion. In certain circumstances, antidotes can save lives or shorten the duration of toxicity or reduce its severity, increasing the chances of recovery in overdosed patients. In recent years, there has been a breakthrough in the field of antidotes resulting in the emergence of a new group of supramolecular antidotes. In 2002, sugammadex was developed to reverse the effects of NMBA overdose. There are side effects of sugammadex worth mentioning such as anaphylaxis (0.039%), bradycardia, bronchospasm and cardiac arrest.
Lipid emulsions are IV lipid emulsions used as dietary supplements in patients who cannot consume enough fat in their diet during illness or surgery. But these lipid emulsions have been found to be effective in treating severe cardiotoxicity caused by IV overdose of local anaesthetic such as bupivacaine[19].They have also emerged as potential rescue therapy for other acute toxicities and poisoning caused by drugs such as tricyclic antidepressants, calcium channel blockers, beta blockers, antipsychotics, insecticides and organophosphorous compounds.
Acetylcholine reactivators are shown to be able to reactivate diethylphosphoryl ACh esterases.
CaCl2 is a compound that can neutralise or reduce the toxic effects of beta blockers and calcium channel blockers. In case of beta blockers,1000 mg is given IV bolus via central line[20]
Dantrolene comprises odourless and tasteless crystals and is direct acting skeletal muscle relaxant that specifically targets muscle cell intracellular calcium release channels called ryanodine receptors. It decreases excessive calcium release from sarcoplasmic reticulum that leads to muscle relaxation by preventing muscle contraction triggering. It also obtains normal Mg++ sensitivity of Mg++ to MH –susceptible muscle fibres.
Conclusion and future:
All anaesthetic plans should include consideration of factors that may delay recovery in a particular patient, these include:
- Proper pre-op assessment done and any problem with anaesthetic history highlighted.
- Expert opinion of colleagues is valuable.
- Discuss factors of concern with the surgeon.
- Premedications avoided.
- Consider short acting agents such as remifentanil,remimezolam,propofol and desflurane.
- Monitoring such as Temperature, BIS and Nerve stimulator to optimise anaesthetic drug doses.
- Reversal agents used with appropriate doses.
- Multimodel analgesia i.e. RA/infiltration LA,paracetamol,NSAIDs±opiates
- Non-drug management of PONV e.g. acupuncture
- Antidotes kept ready in case if needed.
Modafinil is a wakefulness drug approved for patients with excessive daytime sleepiness associated with narcolepsy. The effect of a single dose of modafinil 200mg and placebo in patients while recovering from GA were evaluated. Modafinil was shown to significantly reduce fatigue and improved feelings of alertness and energy in post-operative patients. Patients recovering from GA can significantly benefit from modafinil administration[21].
We don’t usually think of caffeine as a drug, but it is one of the most widely used drug in the world.
Caffeine has been shown to accelerate recovery from general anaesthesia, this has been shown to work via multiple pathways[22], Ref. Journal of Neurophysiology,2017.
Declaration of Interest: None declared
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Authors:
Dr.Sher Mohammad,Consultant Anaesthetist(retired),STH NHS FT Sheffield
Dr.Parhaizgar Khan,Professor of Anaesthesia,Pakistan International Medical College,Peshawar
Dr.Tariq Mahmood,Assistant Professor Anaesthesia,Sialkot Medical College,Sialkot Pakistan
Dr.Diwan Syed Irfan Ahmed,Consultant Anaesthetist,THQ Hospital,Ahmedpur East,Bahawalpur Pakistan
Dr.Syed Irfan Ali,Medical Officer Anaesthesia Saidu of Group of Hospitals,Swat Pakistan
Dr.Gul Rukh,year-2 Trainee Anaesthetics,Khyber Teaching Hospital,Peshawar, Pakistan
Dr.Sibghat Ullah Khan,Cnsultant anaesthetist,Women Wellness and Research Centre,Hamad Medical Corporation Doha,Qatar.
Dr.Salman Yahya,Locum Consultant Anaesthetist York and Scarborough Teaching Hospitals NHS Foundation Trust
Corresponding Address: smyousafzai@doctors.org.uk
Image: Canva
