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Perianesthetic Pharmacology. Drug Apps. Epocrates http://www.epocrates.com Medscape http://www.medscape.com/public/mobileapp Drugs.com http://www.drugs.com/mobile.html. Anesthetic Agents. Inhalation agents (IAs) CNS is the target system.
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Drug Apps • Epocrates • http://www.epocrates.com • Medscape • http://www.medscape.com/public/mobileapp • Drugs.com • http://www.drugs.com/mobile.html
Anesthetic Agents • Inhalation agents (IAs) • CNS is the target system. • Depresses the reticular activating system, which causes unconsciousness. • Alters neuronal excitability throughout the CNS.
General Effects of IAs • CNS • Cause unconsciousness through depression of excitable tissue at all levels. • Decrease ICP through vasodilatation. • Hyperventilation counteracts this by causing hypocarbia and vasoconstriction.
General Effects of IAs • Cardiovascular • Depressant effect on the myocardium and vasculature. • cardiac output, PVR, and SVR. • Variable effect on the heart rate.
General Effects of IAs • Respiratory • Bronchodilatation. • Affects the ventilatory control. • Dulls the response to a rising CO2. • This effects continues into the postop period.
General Effects of IAs • GI – decreased motility. • Mild to moderate relaxation of skeletal muscle. • Temperature regulation • Hypothalamic regulation is diminished. • Body’s effector mechanisms (shivering, vascular control, behavior choices) are inactivated.
Fluothane – halothane • Introduced in 1956. • Sweet, non-irritating odor. • Rapid onset. • Slow arousal. • High incidence of postop shivering. • Sensitizes the myocardium to adrenergic agents ventricular ectopy, VT and V fib.
Fluothane – halothane • 60-80% excreted unchanged by the lungs. • Rest is metabolized by hepatic microsomal enzymes. • Halothane hepatitis – caused by a metabolite that attaches to the liver and causes the body to not recognize the liver as “self”. • Is a trigger for malignant hyperthermia.
Forane - isoflurane • Has a pungent odor. • Not used for induction, but for maintenance of anesthesia after induction with IV agents. • Excellent skeletal muscle relaxation. • Eliminated almost exclusively by the lungs. • Higher incidence of PONV. • Postop shivering may be increased due to intraop vasodilation.
Suprane - desflurane • Newest inhalation anesthetic. • Used for maintenance of anesthesia. • Rapid onset and offset. • Rapid offset leaves no lingering analgesia; must be supplemented. • Is an airway irritant. • High incidence of breath-holding, apnea, coughing, and increase in oral secretions. • Not used in children, as it has a high incidence of laryngospasm.
Ultane - sevoflurane • Is non-irritating to the respiratory tract, and has a pleasant smell. • Can be used for induction and maintenance of anesthesia. • Fast onset and offset, but not as fast as desflurane. • Rapid offset leaves no lingering analgesia; must be supplemented. • Does not sensitize the myocardium to adrenergic agents. • Fluoride metabolites – use with caution in renal dysfunction.
SevoFlo • Unlike many other inhalation anesthetics, which have a pungent or irritating odor, SevoFlo smells sweet, similar to fruit-flavored chewing gum. Your pet . . . will fall asleep quickly and with minimal stress. When the medical procedure is complete, your pet will usually begin waking up within a few minutes.
Waste Anesthetic Gases in PACU • Most inhalation agents and nitrous oxide are excreted unchanged by the lungs. • Prolonged exposure reproductive and neurologic problems, liver and kidney disease.
Diprivan - propofol • Is a sedative-hypnotic in a class by itself. • Is a milky emulsion composed of eggs and soy. • Effects: • Rapid induction with frequent apnea. • No analgesia. • Rapid offset, with minimal PONV. • Not a triggering agent for MH.
Diprivan - propofol • Less hangover • Pts are responsive earlier • Less PONV • Pts more alert and can eat and drink earlier • Less psychomotor impairment – earlier ambulation
Ketamine - Ketalar • Produces dissociative anesthesia. • Feeling of dissociation from environment. • Used for induction and maintenance of anesthesia. • Intense analgesic properties. • Almost half of pts over 30 yo exhibit delirium or excitement on emergence. • Can induce hallucinations.
Stages of Anesthesia • Stage IV: Medullary depression • Overdose of anesthetic. • Stage III: Surgical anesthesia • Cessation of spontaneous respirations • No reflexes.
Stages of Anesthesia • Classic reference points. • Stage II: Stage of delirium • Hallmark is involuntary activity. • High risk of aspiration, laryngospasm, bronchospasm. • Dysphoria, restlessness, muscle rigidity, urinary and fecal incontinence, BP and HR. • Stage I: Stage of analgesia • Can follow simple commands. • Protective reflexes are intact.
Reflexes as a guide to depth of anesthesia • Reflexes come back in this order: • pupillary lid or corneal reflex swallow cough
Neuromuscular Junction • Nerve impulse causes release of acetylcholine (ACh) into the synaptic cleft. • ACh diffuses across the synaptic cleft, and binds on the post-synaptic fibers of a muscle fiber. • Results in a membrane depolarization, and a muscle contraction.
Neuromuscular Junction • ACh is rapidly broken down by acetylcholinesterase (AChE), which is stored on the muscle fiber. • In addition, ACh is no longer released. • The muscle contraction is terminated.
Depolarizing Muscle Relaxant • succinylcholine – Anectine – Quelicin - Sucostrin • Is the only DMR in use in the US. • Works in 1-1.5 min., and wears off in 4-8 min. • A molecule of sux is 2 linked molecules of ACh. • Works as an agonist; occupies the receptor and stimulates it is exhausted.
Succinylcholine • Effects: • Paralysis and apnea. • No effect on CNS. • No analgesia. • Fasiculations. • Myalgias.
Succinylcholine • Effects: • Hyperkalemia in susceptible pts. • Can cause cardiac standstill due to hyperkalemia. • Is a triggering agent for MH. • Avoid in children for this reason.
Succinylcholine • Is broken down by pseudocholinesterase, also called plasma cholinesterase (PC). • This enzyme can be under produced or absent; this deficit is genetic, and runs in families. • PC and serum albumin tend to be directly related. • Sux in the absence of PC will result in paralysis that lasts for several hrs to a day.
Non-Depolarizing Muscle Relaxants • NDMR occupy the cholinergic receptor on the muscle fiber, resulting in paralysis. • ACh is still released, and competes for the binding site.
Non-Depolarizing Muscle Relaxants • Paralysis occurs from fine to gross movement. • As the pt recovers from the paralysis, it progresses from gross to fine movement. • Sequence of return: • Diaphragm intercostal muscles limbs & neck hands jaw eyes
Non-Depolarizing Muscle Relaxants • Effects of NDMR • Paralysis with apnea. • No effect on CNS. • None of the effects seen with sux, i.e., fasciculations, myalgia, hyperkalemia. • No analgesia. • Onset is variable, but averages several minutes. Offset depends on the agent; can be 20-30 minutes to 4-5 hours.
Curare • Comes from an arrow poison used in the Amazon. • First discovered by the Europeans in the 16th century. • First used in the US in the 1940s. • Causes histamine release. • Is cumulative, and can cause reparalysis, or recurarization. • Not commonly used.
NonDepolarizing Muscle Relaxants • Tracrium – atracurium • Intermediate acting • Hoffman degradation • Nimbex – cisatracurium • Intermediate acting • 80% by Hoffman degradation • Pavulon – pancuronium • Long acting • Histamine release
NonDepolarizing Muscle Relaxants • Zemuron – rocuronium • Short acting • Onset 1 min; offset 15-20 min • No histamine release • Norcuron – vecuronium • Intermediate acting • No histamine release • No CV effects – useful in cardiac surgery
Awareness During Anesthesia • Incidence of 0.1-0.2%. • Very frightening experience. • One-half are reported in PACU. • 70% experience post traumatic stress syndrome: sleep disturbances, nightmares, panic attacks, flashbacks, avoidance of medical care.
Awareness During Anesthesia • Higher incidence during C-sections, cardiac surgery and trauma. • Lighter anesthesia is used due to limited cardiac reserve, hypovolemia, hypotension, or fear of decreasing the uterine tone and increasing blood loss. • Higher incidence with total IV anesthesia. • Lower incidence with inhalation anesthetics.
BIS Monitor • Bispectral Index Monitor. • Is an EEG-based monitor of anesthetic effect. • Is used as an indicator of the level of sedation. • Can greatly eliminate intra-operative recall. • Used as an indicator to the depth of anesthesia.
Items for Further Review • Specific muscle relaxants • How they are metabolized • How long they last • Specific uses
NDMR Reversal Agents • Are anticholinesterase agents. • Block the enzyme AChE, resulting in more Ach in the neuromuscular junction. • Results in reversal of the paralysis, and normal muscle contraction.
NDMR Reversal Agents • Also cause: • Bradycardia, CO. • Bronchoconstriction. • GI peristalsis: urination, defecation. • To counteract these effects, must co-administer an antimuscarinic agent. • Atropine • Robinul - glycopyrrolate
Effects of Antimuscarinics • HR. • Inhibit peristalsis and micturation. • Cause mydriasis. • Atropine crosses the blood brain barrier, and can cause a central anticholinergic syndrome. • Robinul does not cross the BBB.
Anticholinergics • Neostigmine - prostigmine • Enlon - edrophonium • Enlon Plus – edrophonium and atropine • Regonol - pyridostigmine • To reverse a block, must have some recovery of muscle function.
Inadequate Muscle Strength • Pt can be brought to PACU not fully reversed. • Pt can be WNL on admission to PACU, and reparalyze. • It is rare, but could happen in OPS. • Ask the pt to hold head up x 5 sec. • Very frightening experience.
Malignant Hyperthermia • Rare, potentially fatal disorder of skeletal muscle triggered by certain anesthetic agents. • Before 1970, mortality was 70%. • Dantrolene was introduced in 1979; now the mortality is 6-7%.
Malignant Hyperthermia • MH is an autosomal dominant genetic trait, and runs in families. • Ask this question in anesthesia questionnaires. • Incidence is 1:20000 to 1:50,000 in adults, and 1:15,000 in children. • Many cases undetected • Never anesthetized • Short anesthetic period
Triggering Agents • All inhalational anesthetics • halothane • isoflurane • desflurane • sevoflurane • Succinylcholine • NOT triggering agents: • All muscle relaxants EXCEPT sux • Propofol • Nitrous oxide
Diagnosis • No lab test for MH. • Must obtain a thumb-sized skeletal muscle biopsy from the thigh that can only be done at 4 hospitals in the US, and 1 in Canada. • Cost is $6000 to $10,000. • Muscle contracture testing. • Genetic testing can be done at 2 hospitals in US.
Clinical Presentation • Triggering agent release of abnormal amounts of calcium from skeletal muscle. • Results in sustained skeletal muscle contraction. • Subsequently causes hypermetabolism, muscle injury and muscle rigidity. • Increased O2 consumption and CO2 production precede hyperthermia.
Initial Signs and Symptoms • Increasing ETCO2 • Tachypnea and tachycardia • Hypoxemia • Muscle rigidity • Trismus – masseter muscle rigidity