Intraveous anesthetics

Dr.Hussam Alsharani Dr.Osama IbrahimAnesthesia resident Assistant professorAnesthesia d. KKUH Anesthesia d. KKUH

Ideal IV anesthetics:1-Drug compatibility (water solubility) and stability in solution.2-lake pain on injection , veno irritation , and local tissue damage.3-low potential to release histamine.4-rabid and smooth onset of action without excitatory activity.5-rabid metabolism to inactive metabolites.6-a steep dose to minimize titratability and tissue accumulation.7-lake of acute cardiovascular and respiratory depression.8-decrease in cerebral metabolism and intracranial pressure.9-rabid and smooth return to consciousness .10-abcense of post operative nausea , vomiting, amnesia , psychoimetic reaction , dizziness , headache , and prolonged sedation.

Pharmacokinetics:Anesthesia is produced by diffusion of drug from arterial blood across the blood brain barrier in to the brain which regulated by the following factors:-protein binding: unbound drug is free to cross BBB.-blood flow to the brain.-extracellular PH and Pka of the drug: nonionized.-solubility of the drug in lipid and water: high lipid solubility enhances transfer in to the brain.-speed of injection.

Barbiturates (Thiopental):-available as sodium salts (yellowish powder).-bitter taste + smell of garlic.-solution of thiobarbiturates are stable for 2 weeks.-ph of solution of thiopental (2.5%) is 9.-does not cause pain on injection.-metabolized in liver to hydroxythiopental and carboxylic acid.-produce anesthesia in less than 30 sec after iv injection.-induction dose: 3-5 mg/kg in adults 5-6 mg/kg in children 6-8 mg/kg in infants-recovery after 10 min

-produce decrease in CPF there by lowering ICP.-widely used to improve brain relaxation during neurosurgery and to improve cerebral infusion pressure after acute brain injury-It cause dose dependent anticonvulsant activity.-dose dependent respiratory depression.-it cause decrease in cardiac output and ABP.-early absence in eyelid reflex.

-tissue necrosis: median nerve damage may be occur after extravenous injection in the antecubital fossa if perivenous injection occurred the needle should be left in place and injection of hyaloronidase.-intra-arterial injection: pt usually complains of burning pain + intense in this case: -stop injection. -leave needle in artery. -administrate papaverine 20 mg. -heparin should be given iv and orally. -stellate ganglion or brachial plexus block may reduce arterial spasm.

Propofol:-(2,6-dispropylphenol).-pain on injection 32-67% of patients.-t1/2 is 1-8 min (Barash 2009).

-elimination half time 2-24 min.-metabolized in liver to sulfate and glucuronic acid which are eliminated by kidney.-extra hepatic rout of elimination by lungs.-anesthesia is induced in 20-40 sec after iv administration.-we can monitor the onset by loss of verbal contact.-induction dose 1.5 – 2.5 mg/kg.-children require bigger dose.-euphoria effect.

-propofol decrease CPF and ICP.-excitatory motor activity without EEG changes.-dose and concentration dependent cardiovascular depression.-dose dependent respiratory depression with apnea.-antiemetic effects (10-20 mg to treat nausea and emesis in the early post operative period.-antidopamenergic which lead to euphoria.-it decrease the pruritus produced by spinal opioids.-agent of choice in malignant hyperthermia suspictable pt.-Propofol syndrome : after high dose infusion of propofol for long time – myocardial failure – metabolic acidosis – rabdomyolysis.

Propofol has no effect on bronchial muscle tone and laryngospasm is particularly uncommon .The suppression of laryngeal reflex and low incidence of coughing or laryngospasm when a laryngeal mask airway (LMA) is introduced , and propofol is regarded by most anesthetists as the drug of choice for induction of anesthesia when LMA is to be used.

Etomidate:-carboxylated imidazole.-ph 6.9 , pain on injection , venoirritation.-induction dose : 0.2-0.3 mg/kg.-involuntary myoclonic movement are common at induction.-metabolism in liver.-it decrease CPF and ICP.-inhibitory effect on adrenocortical synthetic function (5-8 h after single use)-inhibit platelet function.-minimal cardiorespiratory depression .-does not induce histamine release.-high incidence of post op nausea and emesis .

Absolute contraindication: -airway obstruction. -prophyria. -adrenal impairment. -long term infusion in ICU (increase infection and mortality).

Kitamine:-Arylcyclohexylamine.-water soluble compound.-potent anesthetics and analgesic properties +amnesia .-metabolized by liver to norkitamine which excreted by kidney.-elimination half life 2-4 h .-dose dependent CNS depression + stimulation of limbic s.-induction dose: 1-2 mg/kg IV. 4-8mg/kg IM.-duration of action: 10-20min –full orientation require more 60 – 90 min

-high incidence of psychomimetic reactions (namely , hallucination , nightmares , altered short term memory , and cognition).-ketamine increase CPF and ICP .-bronchodilatory activity - minimal respiratory depression.-increase oral secretion.-cardiovascular stimulation + increase peripheral resistant.-not recommended in severe coronary artery disease.-increase pulmonary artery pressure (contraindicated in poor right ventricular reserve.

Indications: -high risk pt: shocked patients. -pediatric anesthesia. -difficult locations: site of accidents. -developing countries: where anesthetic equipment and trained staff in short supply.

Benzodiazepines:-medazolam , lorazepam , diazepam and antagonist flumazenil.-metabolized in liver , excreted by kidney.-short acting: midazolam - flumazenil.-intermediate: diazepam.-long acting: lorazepam.-only midazolam can given by continuous infusion.-all benzodiazepines produce: anxiolytic, anterograde amnesia, sedative, hypnotic, anticonvulsant, and spinally mediated muscle relaxant properties.

-dose dependent respiratory depression.-it depress the swallowing reflex and depress upper airway reflex activity.-produce decrease in systemic vascular resistant and blood pressure in large doses.-specific antagonist :flumazenil

Dexmedetomidine:-alpha 2 adreno receptor agonist.-approved by FDA for the short term less than 24 h sedation of the mechanically ventilated pt in ICU.-unique type of sedation-analgesia with less respiratory depression + amnestic affect .-it produce hypotension and bradycardia more than diazepines.-infusion rate 0.2-0.6 mcg/kg/h.-improve post op pain control after major surgery.-slower onset and offset than propofol , sedation like midazolam. -high cost.

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