General Anesthesia

Balanced Anesthesia

General anesthesia, or more simply “anesthesia,” consists of a state of induced, reversible, and controlled unconsciousness (“hypnosis”) and painlessness (“anesthesia”) often referred to as “balanced anesthesia.” This state is controlled and adjusted by anesthesia personnel using various anesthetic agents to allow surgical or other invasive procedures to be performed under “sleep and painlessness.” Previously, the main components used for balanced anesthesia included a hypnotic (sleep-inducing) agent for induction, an anesthetic for maintenance (inhalation anesthetics), an analgesic (a strong opioid), and a muscle relaxant. These four agents form the basis of anesthesia, and how they are used and controlled safely and effectively is the essence of balanced anesthesia.

Anesthesia for surgery can be divided into four different phases: induction, maintenance, emergence, and recovery. The first three phases usually occur in an operating room, while the recovery phase mainly takes place in a recovery room, postoperative ward, or intensive care unit. The management of anesthesia through these phases with various anesthetic agents is described here in the Anesthesia Guide. You can find several management cards with different variants of anesthetic agents for balanced anesthesia here.

The use of anesthetic agents has changed in recent years, but the goal of balanced anesthesia remains to induce a state of controlled unconsciousness where the surgeon can perform the procedure under optimal conditions and maintain the patient’s various organ functions as best as possible. The role of the anesthesiologist is to maintain “good homeostasis” during the patient’s controlled unconsciousness.

Hemodynamic effects of Anesthetics

Good homeostasis means maintaining a constant internal environment that is compatible with the normal function of the organism, despite external influences. This includes vital parameters such as pulse, blood pressure, temperature, extracellular fluid volume, blood volume, cardiac output, macro- and microcirculation, osmolarity and electrolyte concentration, as well as concentrations of hydrogen ions (pH), glucose, oxygen, and carbon dioxide. We must compensate for blood and fluid losses and maintain normal physiological conditions in the patient as much as possible. The patient must be able to be placed in an unconscious state without movement for many hours in an unnatural manner. The anesthesia and depth of unconsciousness must be adequate and under control throughout the procedure. The patient should never be too lightly or too deeply sedated, and the state must be reversible in a controlled and safe manner.

Balanced anesthesia is managed by balancing physiology and pharmacology under the external influence of surgery, invasive procedures, or other trauma. During anesthesia, we mainly work with circulatory physiology and respiratory physiology, but other functions such as the immune system and hormonal systems affected by general anesthesia are also considered.

Providing balanced anesthesia requires adequate monitoring of the patient’s wakefulness and physiology – good monitoring. The level of monitoring is adjusted according to the nature and duration of the procedure and the patient’s condition and underlying state. Patients in good condition with ASA class I generally do not need the same monitoring as a patient with ASA class IV. Larger and more extensive surgical procedures naturally require more comprehensive monitoring than simple surgical procedures. Older and frail patients generally require more monitoring than young, strong patients, but not always. Typically, monitoring and setup are standardized according to the procedure and then adjusted according to the individual patient. Each specific procedure at each hospital has a specific “set-up” described in special PMs or cheat sheets.

Setup on the operating table

The setup of the patient under anesthesia must be managed, i.e., creating good conditions for the surgeon to work while ensuring the patient can endure an unnatural body position for sometimes many hours without harm, such as compartment syndrome, pressure sores, lung atelectasis, bladder tamponade, or neuralgia (loss of sensation). The setup of a patient under anesthesia is a shared responsibility between the surgical side and the anesthesia side. As far as possible, the setup is done while the patient is awake, but some parts are done while the patient is anesthetized. Some setups in special positions can only be maintained for a limited time; for example, the Trendelenburg position with elevated legs may risk insufficient circulation in the lower extremities if it persists too long.

The brachial plexus is a large nerve plexus formed by the lower cervical spinal nerves and the first thoracic spinal nerve. The plexus passes between the clavicle and the first rib, ending in the axilla, dividing into four large branches. The nerves to the arm originate from the radial plexus. Overextension of the arms, as well as stretching and rotation of the neck, can damage the brachial plexus. Pressure in the axilla and against the neck/shoulders must be avoided.

The peroneal nerve in the lower leg is unprotected and only covered by skin when it curves around the fibular neck on the outside of the lower leg just below the knee. It is very sensitive to pressure and stretching in this area. Keep this in mind if the patient’s legs “fall out” significantly, and it is a long operation. Pressure can cause damage and foot drop and must be prevented in all ways.

Pad between the anesthesia arch and the upper arm when fixing the arm to the arch. Always check that there is no pressure against the patient’s arm. The safety strap that fixes the patient’s leg should be placed a bit above the knee, always padded.

Monitoring during anesthesia

The foundation of monitoring during anesthesia is continuous measurement of vital parameters such as pulse, blood pressure, ECG, and oxygen saturation. Muscle tone is also measured when using muscle relaxants (TOF). This is supplemented as needed with more invasive monitoring, such as continuous intra-arterial blood pressure via an arterial catheter, central venous pressure, BIS, and other central hemodynamics measurements. Part of the monitoring is described as non-invasive monitoring, i.e., without penetrating needles, and invasive monitoring, e.g., with an arterial needle and CVK. More about monitoring is described elsewhere in the Anesthesia Guide.

Inhalation Anesthesia

The method of inducing anesthesia in humans with gas, general anesthesia, has a long tradition and several different anesthetic gases have been used over the years. Usually, halogenated derivatives of ether (inhalation anesthetics) are used alone or in combination with nitrous oxide to induce a controlled form of unconsciousness – anesthesia. Vaporized anesthetic gases such as isoflurane and sevoflurane have a small therapeutic window, so overdosing must be avoided and the amount of gas administered must be precisely controlled via a vaporizer. Inhalation anesthesia has the advantage over intravenous anesthetics that the patient’s end-tidal concentrations/partial pressures can be continuously measured in the exhaled air, which in turn reflects the levels in the blood and brain. The patient’s need for anesthetic agents is indeed age-dependent but also highly predictable with small inter-individual variations.

The potency of anesthetic gases is expressed using the MAC concept (MAC = minimal alveolar concentration). The MAC concept was introduced in 1965 and is expressed as a percentage of the anesthetic gas at 1 atmosphere of pressure (ATM). MAC expresses the minimum alveolar concentration that prevents movement in response to a defined stimulus, such as a skin incision, in 50% of a population (test animals, subjects, or patients). MAC is a measure for comparing the potency of the same anesthetic gas between different populations or the effect of different anesthetic gases on a given population. Another measure of gas potency is MAC-awake (0.3-0.5 MAC), the concentration required to block voluntary reflexes and perceptive awareness. An advantage of inhalation anesthesia is that in the event of an accidental overdose, the administered gas can be easily eliminated through the patient’s exhalation, providing good controllability during ongoing anesthesia.

The depth of anesthesia is primarily monitored using clinical parameters, but technical equipment for monitoring the depth of anesthesia is improving and becoming more common in clinical practice. Normally, the anesthetic gas is dosed according to MAC to achieve a MAC of 0.6-1.0 when remifentanil is given in continuous infusion. If fentanyl is added to the gas instead, and gas is used primarily, the MAC is usually between 0.8 and 1.4. The vaporizer for the anesthetic agent is dosed in percentage, but the effect is read in MAC. At approximately 2 MAC, spontaneous breathing stops, and at 3 MAC, the heart fails, and circulation collapses. The simultaneous use of nitrous oxide reduces the need for vaporized gas and thus increases the safety margin. Roughly, the effect of two combined gases is additive. However, the use of nitrous oxide has significantly decreased in recent years for various reasons and is now mostly used for induction of inhalation anesthesia in children and during labor analgesia. For prolonged anesthesia, a constant MAC results in a progressively higher concentration in the brain, so the MAC should be adjusted down over time. The need for opioids and muscle relaxants is significantly reduced during inhalation anesthesia, which can be an advantage.

Inhalation anesthesia can be divided into controlled ventilation anesthesia and spontaneous breathing anesthesia. Spontaneous breathing anesthesia, where muscle relaxants are not used, is possible with gases administered via a breathing mask, laryngeal mask, or endotracheal intubation. Since the pressure gradient over a laryngeal mask is lower and thus the risk of gas leakage is less compared to mask anesthesia, intubation is less often required. Spontaneous breathing is not only physiological, but it also automatically ensures the correct depth of anesthesia compared to controlled positive pressure ventilation. If the depth of anesthesia is not correct, i.e., if the anesthesia is too deep or too shallow, it simply does not work and it is noticeable in the patient. How to note too deep or too shallow anesthesia is somewhat of an art and requires some experience from the anesthetist. Anxiety in the patient can be due to both too shallow and too deep anesthesia. An unsatisfactory airway never allows for good anesthesia and adequate depth of anesthesia. A free airway is therefore crucial in spontaneous breathing anesthesia, which can sometimes be challenging both in mask anesthesia and laryngeal mask anesthesia. The airway is not even guaranteed to be free when the patient is intubated. Anesthesia depth monitoring can help but is not always reliable.

Since the concentration of anesthetic gas is measurable and the depth of anesthesia is predictable, there is not always a need for other anesthesia depth monitoring such as BIS or “Entropy” in spontaneous breathing anesthesia. However, anesthesia depth monitoring can be a useful tool to avoid too deep anesthesia and too slow awakening.

The time for awakening depends on the solubility of the gas/gases in the tissues and the amount of inhalation anesthetic administered. Desflurane has about half the solubility of sevoflurane, which in turn is half as soluble as isoflurane. Nitrous oxide is significantly less soluble, especially in fat compared to vaporized gases. Modern anesthetic gases provide a quick and predictable awakening, compare “MAC awake”.

During the 1990s, great efforts were made to introduce day surgery into clinical practice. This was primarily for cost efficiency and faster discharge. It then became interesting to use short-acting anesthetic agents to quickly wake up and send home patients after surgery. Previously, sevoflurane and desflurane had been considered unsuitable due to a high rate of metabolism with fluoride formation and a boiling point at room temperature. The pharmaceutical industry invested heavily in documentation and marketing of these two gases. This contributed to increased knowledge and interest in inhalation anesthesia in general.

Over decades of use, it has been found that nitrous oxide can cause the expansion of gas-filled cavities, inhibition of vitamin B metabolism (clinically relevant primarily when anesthetizing vegans and in certain rare genetic inborn errors of metabolism), a slight increase in the frequency of postoperative nausea, and diffusion hypoxia (which presupposes hypoventilation and/or air breathing without oxygen supplementation). Presumed negative effects on the immediate environment and greenhouse effects in the atmosphere also led to a desire to eliminate nitrous oxide from the hospital environment. Since nitrous oxide in combination with another vaporized gas constitutes roughly half the depth of anesthesia, the elimination of nitrous oxide would result in significantly higher consumption of sevoflur ane and desflurane.

Today, sevoflurane is mainly used in clinical practice in Sweden, but desflurane has also gained widespread use. The initially feared risk of kidney damage from sevoflurane has fortunately not been realized. Both “compound A” from the carbon dioxide absorber in the circle system and fluorides from metabolism could theoretically be nephrotoxic. Ironically, the old combination of isoflurane/nitrous oxide provides a faster awakening than a pure sevoflurane anesthesia. The supposedly fast awakening was the main point during the launch of sevoflurane. An advantage, especially in pediatric anesthesia, is that gas induction is easier to carry out with sevoflurane. The patent period for sevoflurane and desflurane has expired and inhalation anesthesia is no longer a hot topic, so alternative but not necessarily better anesthesia methods for the patient have gained ground.

Anesthesia Induction

Induction – Anesthesia Start

Induction, i.e., the start of anesthesia, means putting the patient to sleep, or more correctly into a controlled state of unconsciousness (anesthesia). Intravenous induction is the standard for most anesthetic procedures. The path to it goes through altered consciousness in various stages, different depths of anesthesia at different speeds depending on the technique used. After administering anesthetics, one usually goes through a short stage of relaxation and disinhibition, then a short stage of excitation, and then into the stage often called surgical anesthesia with muscle relaxation and reduced or ceased breathing.

During induction, breathing, consciousness, eye movements and coordination, pupil size, reflexes, muscle tone, and other essential physiological functions are affected. It is important to try to go through the induction stage as smoothly as possible without pronounced effects on pulse and blood pressure. One should try to avoid pronounced blood pressure drops, but a slight drop in blood pressure is common, and most patients who are not significantly heart and vascular sick tolerate this well. When inducing frail patients, it is appropriate to simultaneously administer a blood pressure-raising agent to counteract the blood pressure-lowering effects of the anesthetics.

The induction usually starts with preoxygenation with oxygen via a mask with the patient in the “sniffing position” to prepare for taking over the patient’s breathing and laying down a laryngeal mask or endotracheal intubation. When the patient is well-oxygenated, one either initiates through intravenous injection of anesthetics or through inhalation on a mask of an inhalation anesthetic agent, an “anesthetic gas.” Intravenous induction is usually faster, more controlled, and more predictable than initiation by mask via inhalation.

Induction with Intravenous Induction Agents

Intravenous induction with fast-acting anesthetics is standard in most anesthetics, both for children and adults. The anesthesia is prepared with good premedication, if needed, topical anesthesia (skin numbing), and the insertion of a venous cannula in a peripheral vein (“placing a needle”). After standardized preparations in the operating room and check-in, anesthesia starts with injections of fast-acting sleeping agents administered either manually through a peripheral venous cannula or via infusion pump or a combination of manual injections and infusion pump injections (syringe pump). In traditional anesthesia, the agents are administered manually through injections with a syringe. It is common to start with a strong opioid such as fentanyl or alfentanil over about two minutes. Then, wait until the patient reacts appropriately to the given dose, which also verifies that the venous access works as it should. In the next step, a dose of a hypnotic agent, usually propofol but also other agents such as pentothal, ketamine, or etomidate, is given. The dose is adjusted according to age, weight, condition, and current state.

Propofol

• Concentration: 5 mg/ml, 10 mg/ml, 20 mg/ml
• Induction dose for anesthesia: 2 mg/kg (children – 2.5-3.5 mg/kg)
• Sedation bolus: 0.5 mg/kg
• Maintenance anesthesia: 4-10 mg/kg/h in decreasing dose, TCI 2-6 ug/ml, Sedation: 0.5-4 mg/kg/h
• Avoid: Anesthesia with TCI for children < 16 years

Thiopental (Pentothal)

• Concentration: 25 mg/ml
• Induction dose for anesthesia: 4-6 mg/kg (70 kg -14 ml)
• Precautions: porph yria, upper airway obstruction, asthma attacks, extravasal and intra-arterial injection

Ketamine (Ketalar)

• Concentration: 10 mg/ml iv, 50 mg/ml im
• Induction dose for anesthesia: 1-2 mg/kg iv, (5)-10 mg/kg im + midazolam 1-3 mg (quiet on the floor)
• Maintenance anesthesia: 0.5-4 mg/kg/h iv in decreasing dose
• Pain relief after surgery: 5-15 mg in bolus
• Maintenance infusion: 0.05-0.5 mg/kg/h
• Precautions: High blood pressure (relative contraindication). In liver failure -> dose reduction

Esketamine (Ketanest)

• Concentration: 5 mg/ml iv, 25 mg/ml im => use half the ketamine dose

In a typical induction, non-depolarizing muscle relaxants are administered when the patient is “sleeping well” after the initial induction, i.e., does not react with a blink reflex or to touch about 1-2 minutes after hypnotics have been given. After administering muscle relaxants, a “timer” is usually started, and the patient is given controlled breaths through manual positive pressure ventilation via a breathing mask and bag. This manual ventilation continues for 90-120 seconds, after which intubation or placement of a laryngeal mask can be performed. After securing the airway, it is checked by auscultation with a stethoscope and by monitoring the exhaled air with end-tidal carbon dioxide measurement.

Afterward, an anesthetic gas, such as sevoflurane or desflurane, is usually introduced, and the anesthesia transitions into the next phase, the maintenance phase. The use of muscle relaxants is determined by whether it helps the surgeon, i.e., if it is necessary to penetrate the abdomen or if the patient needs to lie completely still. Muscle relaxants may also be necessary to ventilate the patient in the best possible way and coordinate with the surgery, for example, during thoracoabdominal procedures.

Mask Induction (“Mask Anesthesia”)

Inhalation via mask induction of anesthetic gas is mainly used in children where an intravenous line (venous cannula) is delayed until the child falls asleep and does not experience pain. This requires a good knowledge of anesthetic gas effects and the ability to manage the airway when the child falls asleep and goes through the different stages of anesthesia induction. During mask induction, the excitation phase is more pronounced and prolonged than with intravenous induction. Usually, one starts with spontaneous breathing to gradually transition to manually controlled breathing while deepening the anesthesia depth with inhalation anesthetics via a vaporizer. One should be gentle but steady-handed as vigorous airway manipulation during the excitation phase can trigger a laryngospasm, complicating the anesthesia induction and making it difficult to deepen the anesthesia depth to the right level. Inserting an oropharyngeal airway can improve the airway and allow manual ventilation so that the excitation stage is passed correctly, while it can trigger a laryngospasm if done when the patient is too lightly sedated. The anesthetic gas must be administered at the right pace, as too rapid administration can cause apnea or laryngospasm or trigger a restless patient. Involuntary uncontrolled movements during this phase are common. Severe excitation can cause significant stress with tachycardia and blood pressure elevation followed by a severe and dangerous blood pressure drop when the excitation passes and should therefore be avoided.

Mask induction in adults is now rarely done but was more common in the past. It can be done in exceptional cases, e.g., for patients with pronounced needle phobia or patients with severe autism. However, it is the author’s personal experience that patients who are so needle-phobic that they refuse intravenous induction may also present difficulties with inhalation induction. The best way to address this problem is usually through good preoperative information and strong premedication, as well as effective topical anesthesia to place a venous cannula. Another reason could be an extremely difficult-to-venipuncture patient who has had enough of multiple needle attempts while awake.

RSI Rapid Sequence Induction

When inducing anesthesia in a patient with an increased risk of airway aspiration of stomach contents, the patient is anesthetized using a technique called RSI: “Rapid Sequence Induction.” With this technique, the head end is placed in an elevated position, known as the “sniffing position.” The patient is pre-oxygenated thoroughly via spontaneous breathing on a tightly fitting mask with 100% oxygen, after which the induction agents are administered in quick succession, including analgesics, hypnotics, and muscle relaxants. The patient is then intubated directly without controlled positive pressure ventilation. Cricoid pressure can be used simultaneously, but this has been questioned in recent years as it can complicate intubation and its benefits are dubious. Examples of cases with increased risk of aspiration include bowel paralysis (ileus) and acute patients who have not fasted long enough.

Maintenance Phase

During the maintenance phase, anesthesia is managed according to the principle of good homeostasis, where anesthesia is adjusted based on the nature and extent of the procedure. Good continuous communication between anesthesia and the surgeon is necessary for this to work well. This is the phase where surgery is performed. Anesthesia is controlled and adjusted based on pulse, blood pressure, temperature, oxygen saturation, extracellular fluid volume, blood volume, and cardiac output. Wakefulness or the degree of unconsciousness is monitored clinically or with anesthesia depth monitors like BIS, Sedline or Entropy, aiming for a value between 40 and 60%, and avoiding too shallow or too deep sleep.

Anesthesia is maintained either with intermittent doses of intravenous agents like fentanyl in combination with an inhalation anesthetic like sevoflurane, or with a continuous infusion of an opioid in combination with an inhalation anesthetic or solely with intravenous agents such as propofol and remifentanil. When using only intravenous agents, the anesthesia technique is called Total Intravenous Anesthesia (TIVA), while the combined technique with inhalation anesthetics is called Balanced Anesthesia. The preferred technique can be guided by the anesthesiologist and is often based on the nature of the procedure and local routines and practices. Some prefer an inhalation-based technique, while others prefer the intravenous technique, and still others prefer the combined technique. Both techniques are well-proven and effective. The degree of administration of anesthetic agents is controlled based on the surgery and the patient’s wakefulness and physiological state. Anesthesia is always a dynamic state with continuous variations, making it an exciting and challenging job. Changes in physiology and settings in anesthesia are continuously documented in the so-called anesthesia chart. The anesthesia chart has traditionally been a paper record continuously written by the anesthesia nurse throughout the procedure from start to finish, but in recent years, more and more information has been digitized, and some clinics use only digital systems. As the operation or intervention under anesthesia approaches its end, the anesthesia is adjusted accordingly, the anesthetic agents are downregulated, and the next phase, the waking phase, begins.

Waking and Extubation

Toward the end of the surgical procedure, anesthesia is adjusted for the patient to wake up from anesthesia. The anesthetic agents are turned down so that their effects wear off and the patient becomes more awake. This is adjusted according to the surgery, and the patient should usually be well anesthetized until the last stitch is placed, or until the patient is turned to the correct position for waking, e.g., from the prone position to the supine position. The surgical wound should be closed, and dressings applied before waking. All sterile surgical attire should be removed in a “draping off” and “undraping,” which usually happens relatively quickly. Infusions, any wound drains, and drips should be adjusted and prepared for the postoperative phase. Patients without a bladder catheter should generally undergo a “bladder scan,” where the urine volume in the bladder is measured and, if necessary, drained before waking from anesthesia. The patient should then be extubated or the laryngeal mask removed, which is done when the patient wakes up and can manage their own spontaneous breathing adequately.

The actual waking process typically involves turning off the anesthetic agents, and the patient wakes up on their own as the anesthetic effects wear off. The anesthetic agents are turned off, and the anesthetic gases are ventilated out according to the end of the surgery. The patient usually wakes up when spontaneous breathing is stable and the MAC value of the gas is down to 0.1%. Alternatively, certain antidotes, such as naloxone, can be given to counteract the effects of opioids, but antidotes are used sparingly to avoid breakthrough pain. Instead, a longer-acting analgesic, such as morphine, is usually given toward the end of the operation to ensure the patient is pain-free when they wake up from anesthesia. Patients who have been anesthetized solely with intravenous techniques generally wake up faster and better compared to those who have received inhalation anesthetics. Reversing the muscle relaxant effects is routinely done toward the end of anesthesia based on clinical assessment or measurement of muscle activity through TOF measurement. Muscle relaxants are usually reversed by administering a cholinesterase inhibitor such as neostigmine in combination with an anticholinergic agent (Atropine/Neostigmine). Alternatively, the antidote sugammadex can be used. The patient is not extubated until adequate muscle strength has returned and the muscle relaxation has been reversed, such as when the patient can squeeze a hand firmly or lift their head off the pillow, and especially maintain good breathing. Insufficient muscle activity can appear as shallow, gasping breathing, described as “like a fish out of water,” which is a potentially life-threatening condition.

When the patient wakes up, they are extubated, i.e., the endotracheal tube or laryngeal mask is removed, and the throat is suctioned to clear mucus. This is done in a controlled manner when the patient can breathe satisfactorily and make eye contact. If the patient is restless with irregular breathing, cannot make eye contact, or has significant airway irritation (apnea), it may be beneficial to give a small dose of propofol 20-40 mg to relax the patient and eliminate more of the anesthetic gases, improving conditions for extubation. Respiratorily, the patient should be able to manage their breathing with a maximum of 5 cm PEEP and 35% oxygen to be safely extubated. After extubation, the patient should be able to maintain their own spontaneous breathing and keep the airway clear even in the supine position. Typically, oxygen is provided through a nasal cannula or breathing mask during the recovery phase.

Criteria for Extubation

• Spontaneous eye opening
• Facial grimacing
• Patient movement other than coughing
• Conjugated gaze
• Purposeful movements
• End-tidal levels of anesthetic gas lower than:
  • Sevoflurane: 0.2%
  • Isoflurane: 0.15%
  • Desflurane: 1.0%
• Oxygen saturation higher than 97%
• Positive larynx stimulation test
• End-tidal volume greater than 5 ml/kg

After surgery on very fragile patients or after major procedures or in the case of respiratory problems, the endotracheal tube is often maintained, and the patient is transferred sedated to the intensive care unit or the postoperative care unit, still connected to a ventilator for later extubation in a more stable condition. If there is uncertainty about whether the patient can be safely extubated, it is better to keep the tube until a later stage, such as if the patient has become hypothermic, is hemodynamically unstable, or is experiencing significant or ongoing bleeding. The transfer of the patient is usually done with a so-called transport ventilator to postop or ICU.

Recovery Phase

Once the patient is awakened from anesthesia and the operation is completed, the patient should be moved under stable conditions to a recovery unit or postoperative unit (“Postop”). The awakening usually occurs in the operating room on the operating table, and the patient is then transferred to their bed, but sometimes the patient is first transferred to the bed and then awakened there. This is done, for example, when the transfer is expected to be painful or when it is important to avoid uncontrolled movements. Conversely, some anesthetics are initiated in the bed instead of on the operating table when the transfer is expected to be painful, such as in acute fractures.

The recovery is usually managed by different personnel than anesthesia staff in a postoperative unit. The time spent in postop is determined by the nature of the procedure and the patient’s condition. Major surgery naturally requires longer time in postop, but this varies from case to case. In the postoperative unit, it is important to continue good monitoring of vital functions such as breathing, pulse, and blood pressure. Postop usually has a large number of patients simultaneously, and it is important that all are well monitored and that any complications are detected and addressed quickly. Examples of serious complications can include apnea or respiratory failure, bleeding, or severe hypotension. Recommended times for postoperative monitoring can be found elsewhere in the anesthesia guide.

In the recovery phase, it is important for the patient to wake up in a safe manner with adequate pain relief. This is provided either intravenously or in the form of blocks with local anesthetics. Many patients come with an epidural anesthesia (EDA) that has either been started or will be started in postop. Any antibiotic prophylaxis should be given, as well as thrombosis prophylaxis at the right time. Any wound drains and gastric drains should be checked to ensure they are functioning and uncontrolled bleeding must be detected in time. Any X-ray examinations may need to be performed. Adjustments of blood pressure-raising and inotropic agents such as norepinephrine infusion are continuously made. Measurement of hourly urine output is done in relevant cases. Nausea may need to be prevented and treated with antiemetics (PONV). Blood gases and laboratory parameters may need to be checked and followed up.

Patients who have undergone major procedures or are unstable after surgery are often awakened in the postoperative unit. Extubation here is similar to that in the operating room, but the patient is usually no longer affected by inhalation agents. The body temperature should be over 36 degrees, and arterial blood gases are often monitored. After completing the recovery phase, the patient can be transferred to a surgical ward for continued care and treatment, or if it is a day surgery, discharged home. Specific routines apply before discharge to ensure this is done in a safe and secure manner.

Muscle Relaxants

Muscle relaxant drugs induce neuromuscular blockade by acting at the neuromuscular junction in striated muscle, which controls muscle strength and breathing. Muscle relaxants are used to facilitate surgery in general surgery, especially laparoscopic surgery, abdominal surgery, orthopedic surgery, neurosurgery, thoracic surgery, or other surgeries where the patient needs to lie completely still or be flaccid. Neuromuscular blockade is also used to gain control over the airway with good intubation conditions and to better ventilate patients with lung disease.

Axons from nerve endings normally connect to muscle fibers via “neuromuscular junctions” in the motor endplate, where neurotransmitter substances are released from presynaptic vesicles to mediate neuromuscular innervation. From these synapses, acetylcholine is released, rushing across the synapse and binding to postsynaptic acetylcholine receptors for activity. Acetylcholine receptors are cholinergic receptors but can also be activated by nicotine, hence they are called nicotinic receptors – nAchR (nicotinic acetylcholine receptor). Nicotinic receptors are a type of ligand-gated ion channel that opens an ion channel when activated. This affects the resting potential so that the next nerve cell becomes prone to depolarization, generating muscle contractions.

Muscle relaxants are usually quaternary ammonium compounds structurally similar to acetylcholine. These bind to the nicotinic receptor’s alpha subunit and block them.

There are two types of muscle relaxants, depolarizing and non-depolarizing. Depolarizing muscle relaxants (succinylcholine) cause initial stimulation, which induces depolarization with muscle fasciculations; it can be said that the muscles are activated and discharged. Thereafter, the receptor is closed for further nerve transmission until the muscle relaxant substance is broken down by the enzyme pseudocholinesterase. Non-depolarizing muscle relaxants bind to the nicotinic receptor and block nerve transmission; muscle activity is usually blocked for at least 30 minutes after induction.

Succinylcholine chemically looks structurally like a double acetylcholine molecule. When administered, initial fasciculations are usually first visible around the eyes, immediately followed by the face and the rest of the body. Succinylcholine is fast-acting with a short duration; the effect usually lasts 5-10 minutes. Succinylcholine is the muscle relaxant that provides the best intubation conditions and the best airway control. It is used not only to facilitate intubation but also to relieve laryngospasm and severe chest rigidity, such as after an overdose of remifentanil. The short duration is due to redistribution from neuromuscular junctions, and the substance is broken down by pseudocholinesterase, which is the same as butyrylcholinesterase and plasmacholinesterase. There is a familial deficiency of pseudocholinesterase, which can cause some patients to have prolonged muscle relaxation from succinylcholine. Usually, however, the effect wears off even in these patients after a few hours; the condition is rare. In these cases, the administration of succinylcholine should naturally be avoided. Prolonged effects of succinylcholine can occur with liver disease, cancer, poor general condition, and the use of other drugs metabolized by cholinesterase.

Succinylcholine has certain side effects, such as potassium release (caution with burns), arrhythmias, bradycardia (young children), postoperative muscle pain, malignant hyperthermia, and histamine release. It should not be given to patients after prolonged immobilization (long stays in ICU!), muscle diseases, burns (after 24 hours), spinal cord injuries, plasma cholinesterase deficiency, malignant hyperthermia, intracranial pressure increases, or uremia. However, in each individual case, the risks must be weighed against the benefits. Establishing a free airway always has the highest priority in unconscious or drowsy patients, and there succinylcholine is the fastest and most effective for good airway control.

Non-depolarizing muscle relaxants are chemically structured as either steroid-based or benzylisoquinoline-based esters. Steroid-based non-depolarizing muscle relaxants include vecuronium and rocuronium, which are relatively similar. Steroid-based agents have a low frequency of allergic reactions, do not cross the placenta, and are metabolized by hydroxylation in the liver. Rocuronium is an intermediate-acting agent with active metabolites, which means some risk of prolonged effect in liver failure. It is metabolized in the liver and excreted via bile. Rocuronium is an alternative to succinylcholine for rapid sequence induction (RSI) in higher doses than normal, 0. 9-1.0 mg/kg. If needed, the effect can be reversed with the specific antidote sugammadex (Bridion).

Pancuronium is an older long-acting agent with relatively high muscarinic activity that is rarely used today. Pancuronium was the standard agent for anesthesiological muscle relaxation until the 1990s.

There are several other non-depolarizing agents pharmacologically categorized as benzylisoquinolines. These agents have relatively low muscarinic affinity. Among these agents are atracurium, cisatracurium, and mivacurium. These agents have a relatively high histamine-releasing effect, which clinically risks causing skin flushing and bronchoconstriction. Atracurium and cisatracurium are broken down by nonspecific plasma esterases and have a spontaneous chemical breakdown via the so-called Hoffman elimination. Mivacurium is broken down by pseudocholinesterase. The elimination is independent of liver and kidney function.

Atracurium is an intermediate-acting non-depolarizing agent with a heterogeneous composition of isomers. Atracurium releases histamine and is eliminated via Hoffman elimination.

Mivacurium is a short-acting non-depolarizing muscle relaxant. It releases some histamine and is broken down by pseudocholinesterase.

Reversal of muscle relaxation

Neostigmine (2,5 mg) and 0.5 mg Atropine

The effect of non-depolarizing muscle relaxants is usually reversed with neostigmine, a cholinesterase inhibitor, thereby restoring muscle innervation. Neostigmine can cause bradycardia and bronchoconstriction, so atropine is usually given simultaneously as an anticholinergic. A typical reversal dose for an adult is 2.5 mg neostigmine (1 ml) and 0.5 mg atropine (1 ml), totaling 2 ml. Neostigmine can increase the amount of acetylcholine in the synapse and compete away non-depolarizing muscle relaxants. If the reversal is incomplete, an additional half reversal dose can be given (1/2 ml neostigmine + 1/2 ml atropine). The dosage of neostigmine is 30-70 mcg/kg, but the dosage is usually standardized to 1 ml (2.5 mg) for adults and adjusted by weight for children. The effect of muscle relaxants and reversal should be continuously monitored with specific monitoring systems.

Sugammadex (Bridion®)

Antidote to non-depolarizing muscle relaxants for intravenous use. Sugammadex is a derivative of gamma-cyclodextrin. Sugammadex forms a complex with the neuromuscular blocking agents rocuronium and vecuronium in plasma, thereby reducing the amount of muscle relaxant available to bind to the nicotinic receptor in the neuromuscular junction.

Dosage: For normal reversal 4 mg/kg, which gives 280 mg (2.8 ml) to a 70 kg patient. For children and adolescents only 2 mg/kg, which gives 80 mg (0.8 ml) to a 40 kg child.

Indication: Reversal of the muscle relaxants rocuronium (Esmeron) and vecuronium (Norcuron). Effect usually occurs within 2 minutes with almost complete recovery of muscle strength.

Vasopressor Support Against Hypotension during Anesthesia

Ephedrine

• Indication: Hypotension, bronchial asthma
• Concentration: 5 mg/ml
• Direct receptor agonist + NA release –> α1 +, β1+++, β2 ++ = SVR↑, CO↑, HR↑, BP↑
• Dosage: 5-10 mg IV – effect 10-15 min (for a longer-lasting effect, 25-50 mg can be given IM or SC)
• Side effects: Tachycardia, arrhythmias, coronary ischemia

Phenylephrine

• Dosage: 0.1-0.2 mg IV, or infusion 0.05-0.15 μg/kg/min IV = approximately 3 – 20 ml/h for 70 kg
• Concentration: 0.1 mg/ml
• Physiological effects: α1 ++++ = SVR↑, CO↓, HR↓, BP↑
• Side effects: Bradycardia, heart failure, pulmonary edema

Norepinephrine

• Indication: Sepsis, anaphylactic shock, hypotension with SVR↓↓
• Physiological effects: α1 ++++, β1+++, β2+ (SVR↑, CO±0, HR↑, BP↑↑
• Dosage: 0.01-0.5 μg/kg/min = 0.5-40 ml/h for 70 kg (0.1 mg/ml)

Anesthesia Methods for Elective Surgical Procedures

Pocket Guide – Anesthesia

Pocket guide with condensed information on inhalation agents, muscle relaxants, inhalation anesthesia, vasopressors, opioids, antiemetics, reversal agents, and malignant hyperthermia.

Standard Anesthesia

Malignant Hyperthermia

Guidelines for Treating an Acute Malignant Hyperthermia Reaction

Malignant Hyperthermia (MH) susceptibility is an inherited condition where potent inhalation anesthetics and/or succinylcholine can trigger a life-threatening reaction during anesthesia. Signs of an MH reaction include hypermetabolism and muscle impact. MH reactions are rare and important to identify as they are potentially life-threatening and treatable. A previous complication-free anesthesia with MH-triggering agents does not rule out MH susceptibility.

Triggers: Celocurin + inhalation gases.

Symptoms: Muscle rigidity, temperature increase of 1°C/5 minutes, EtCO2↑, sweating, tachycardia

Treatment: Hyperventilate minute ventilation x 2-3 with 100% O2, switch to TIVA, disconnect vaporizers, and end the operation.

Dantrium initial dose: 2.5 mg/kg (in large IV/CVK) – repeat 1 mg/kg until temperature decreases.

Agents That Can Trigger an MH Reaction

1. Potent inhalation anesthetics

• Sevoflurane (Sevorane^®)
• Desflurane (Suprane^®)
• Older inhalation anesthetics – Isoflurane, Halothane, Enflurane, Ether, etc.

2. Depolarizing muscle relaxants

• Succinylcholine (Celokurin^® – succinylcholine)

Signs of an MH Reaction

The clinical signs of an MH reaction can vary greatly, from few to many. The course can be anything from explosive to more “creeping.” The clinical diagnosis can therefore be difficult to make. An MH reaction almost always develops during anesthesia or, in rare cases, immediately postoperatively. No symptom is pathognomonic for an MH reaction. The diagnosis of an MH reaction is a diagnosis of exclusion.

Early Signs from Different Organ Systems

Metabolism

Increased metabolism – hypermetabolism (“metabolic storm”)

• Signs of increased CO₂ production (EtCO₂, or pCO₂), tachypnea. The value of CO₂ must be related to minute volume. If capnography is absent, high respiratory rate and rapidly consumed and hot CO₂ absorber suggest increased CO₂ production.
• Increased O₂ -consumption
• Metabolic and respiratory acidosis
• Profuse sweating
• Mottled skin

Musculature

• Masseter spasm after administration of succinylcholine (Celokurin®). Masseter spasm = “jaws of steel” persisting for two minutes or more.
• Generalized muscle rigidity. Generalized muscle rigidity usually comes a little later in the course.

Cardiovascular

• Inexplicable tachycardia
• Arrhythmias (mainly ectopic ventricular beats, VEB in bigeminy)
• Unstable blood pressure

Late Signs

• Rapid temperature increase (core temperature). Measure temperature centrally; rectally, bladder, esophagus, or in CVK. Temperature increase is secondary to hypermetabolism, i.e., high temperature is not a first sign.
• Hyperkalemia. Instant hyperkalemia after administration of succinylcholine also suggests muscle dystrophy, e.g., Duchenne muscular dystrophy
• Sharp increase in CK (creatine kinase)
• Sharp increase in myoglobin (plasma/urine)
• Dark-colored urine (Coca-Cola/port wine-colored) (sign of myoglobinuria)
• Renal failure
• Severe arrhythmias or cardiac arrest
• Disseminated intravascular coagulation
• Multiple organ failure
• Brain death/death

Differential Diagnoses

• Too light anesthesia
• Infection/sepsis
• Insufficient ventilation or insufficient fresh gas flow
• Faulty anesthesia machine
• Iatrogenic temperature increase
• Other neuromuscular disease
• Anaphylactic reaction, pheochromocytoma, thyrotoxic crisis, reaction triggered by ecstasy or other stimulant drugs, malignant neuroleptic syndrome (NMS – Neuroleptic Malignant Syndrome).

Treatment

Treatment should begin immediately. Dantrolene has the highest priority. Delay in administration of dantrolene increases mortality and morbidity. Symptoms can vary significantly and treatment is adapted accordingly.

Immediately

• Stop the administration of all triggering agents. Remove the vaporizer. If it is not possible, turn it off.
• Increase to 100% oxygen and increase fresh gas flows to > 10 liters/min.
• Hyperventilate 2 – 3 times the normal minute volume with 100% oxygen.
• Inform everyone in the room and call for help. Request dantrolene. It requires plenty of personnel to mix dantrolene, take samples, arrange intravenous access, etc.
• Switch to total intravenous anesthesia. Do not waste time here changing hoses or anesthesia machines, this can be done later. Dantrolene has the highest priority.
• Decide whether the surgical procedure should/can be completed or not.
• If the operator is inexperienced, call an experienced colleague.

Dantrolene (Dantrium^®)

• Administer dantrolene 2 mg/kg intravenously. Vials of 20 mg are mixed with 60 ml of sterile water. It is easiest with room temperature sterile water.
• Repeat administration until symptoms subside.
• If it looks like dantrolene shortage, procure more from another healthcare facility.
• The maximum dose of dantrolene is 10 mg/kg, but this dose may rarely need to be exceeded.

Monitoring

• Continue ongoing monitoring (SaO₂, EtCO₂, EKG, Blood pressure).
• Temperature measurement centrally (rectally, bladder, esophagus, or in CVK). Peripheral temperature measurement is unreliable in this situation.
• Ensure good functioning venous access.
• Urinary catheter, arterial line, and CVK may be needed. Administration of dantrolene has a higher priority than CVK and arterial line initially.
• Laboratory tests
• Blood gas
• Electrolyte status
• CK
• Myoglobin
• Blood sugar
• Creatinine
• Liver status
• Coagulation status
• If indicated, other testing
• Monitor/treat the patient in an intensive care or postoperative unit for at least 24 hours after an MH reaction. Symptoms may recur and require treatment.
• Compartment syndrome may develop. Check as needed.

Symptomatic Treatment

Treat Hyperthermia

High priority.

• Administer 2 -3 liters of cold NaCl, Ringer’s acetate, or similar.
• Surface cooling: wet sheets or ice in the armpits and groin.
• Other methods, e.g., surface or intravenous cooling device.
• Stop cooling the patient when the central body temperature drops to ~38 -38.5^o. The temperature will drop further after cooling is stopped. With excessive cooling, there is a risk of rebound phenomenon.

Treat Hyperkalemia

High priority.

• In case of life-threatening hyperkalemia, administer calcium. For example, calcium-gluconate 10-20 ml to an adult.
• Glucose and insulin IV. If needed. e.g., 20 E “rapid insulin” in 1000 ml 5% glucose 100-200 ml per hour. More insulin may be needed. Check for hypoglycemia.
• Dialysis may be needed.

Treat Acidosis

• Hyperventilate to normocapnia, if possible.
• Administer Tribonat^® or Sodium Bicarbonate if pH< 7.2.

Remember that administration of Sodium Bicarbonate increases CO₂ load

Treat Arrhythmias

• Amiodarone (Cordarone^®) 300 mg to an adult (3 mg/kg)
• β-blockers in case of persistent tachycardia
• Do not administer calcium antagonists

Maintain good diuresis > 2 ml/kg/hour with

• Diuretics, e.g., furosemide or mannitol. Note that each vial of dantrolene contains 3 g of mannitol.
• Fluid, e.g., Ringer’s acetate or NaCl.

Patients who have had a suspected MH reaction should undergo an MH investigation with an IVCT test and mutation analysis. IVCT = in vitro contracture test.  This test involves taking a small muscle sample, mounting it in an organ bath, and exposing it to halothane and caffeine, as well as electrical stimulation. Only a negative mutation test does not exclude MH susceptibility. The patient’s closest relatives should be informed.

References

• Glahn KP et al. Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group. Br J Anaesth. 2010 Oct;105(4):417-20.
• Rosenberg H, et al. Malignant hyperthermia: a review. Orphanet J Rare Dis. 2015;10:93.
• Hopkins PM, et al. European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility. Br J Anaesth.2015 Oct;115(4):531-9.
• Hyperkalemia http://www.internetmedicin.se/page.aspx?id= 899 (downloaded 2017-02-26)

There is an app for iPhone that can be helpful:

Appstore: MHapp – Malignant Hyperthermia