Anesthetic Drugs: Midazolam (Versed)

Objectives

• Students will learn to categorize anesthetic drugs by purpose and sequence in anesthetic plans.
• Students will discuss anesthetic medication concentrations and doses for routine inductions on adults.
• Common anesthesia medications and the induction of adult patients will be reviewed.
• Instruction related to anesthesia and induction is in NSG 742A during Summer 1, with NSG 746 covering medications in Fall 2.

Midazolam (Versed)

• Variable concentrations exist, such as 1 mg/ml in 2, & 5 ml vials.
• Variable doses are available, with 2 mg used for pre-op sedation in adults less than 65-70 years old.
• 0.01 – 0.1 mg/kg can be administered in 30-60 seconds; effects last for 60 minutes.
• For pediatric patients, PO is dosed at 0.5 mg/kg; Max 10-20 mg.
• Versed produces anticonvulsant effects, amnesia, & muscle-relaxing properties useful for inhibiting alcohol withdrawal symptoms
• Benzodiazepines produce dose-related anterograde amnesia.
• Midazolam produces synergistic CNS, CV, and respiratory effects with fentanyl.
• Benzodiazepines have minimal cardiovascular effects at commonly used clinical doses.
• Profound hypotension can occur in the volume-depleted patient.
• Midazolam is the most respiratory depressing benzodiazepine.
• Combining benzodiazepines with CNS depressants such as opioids can increase respiratory depression and apnea.

Dexmedetomidine (Precedex)

• The concentration is 4 mcg/ml after Ruby Pharmacy dilution.
• Boluses administered up to 4-8 mcg, or 0.4-0.7 mcg/kg.
• The loading dose is 1 mcg/kg, infused over 10 minutes, followed by maintenance infusions of 0.2 to 0.7 mcg/kg per hour.
• 100 mcg in 9 ml NS = 10 mcg per ml.
• Dexmedetomidine produces dose-dependent sedation resembling natural sleep, without respiratory depression
• The central sympatholytic effects result in antishivering action, hypothermia, and reduced neuroendocrine stress response.
• Postoperative agitation and emergence delirium reduction in children and adults is an increasingly used clinical action of Dexmedetomidine.
• Analgesic- and anesthetic-sparing effects are well documented at both the brain and spinal cord level.
• The main cardiovascular effects are hypotension hypotension and bradycardia due to CNS alpha receptor stimulation and systemic vasodilation.
• Transient hypertension is sometimes seen with rapid initial loading doses, or high maintenance doses due to vasoconstriction, however, dose-dependent hypotension is the norm.

Narcotics: Fentanyl and Remifentanil

• Fentanyl (Sublimaze) concentration is 50 mcg/ml.
• Dosing is widely variable: Premed: 1-2 mcg/kg.
• General administration: 5-15 mcg/kg.
• Remifentanil (Ultiva) must be diluted to 50 mcg/ml.
• Remifentanil available in variable concentrations from 1-5 mg/ml.
• For Remifentanil, infusion only is recommended 0.5-1 mcg/kg at induction, then 0.5-2 mcg/kg/min.
• Variable Morphine concentrations should be diluted to 1 mg/ml.
• Dose titrate 0.1 mg/kg Morphine for surgical pain.
• Variable concentrations of Hydromorphone (Dilaudid) should be diluted to 0.1 mg/ml usually.
• Administer and label Hydromorphone precisely.
• Titrate Hydromorphone 5 to 10 mcg/kg given for surgical pain.

Induction Agents: Propofol, Etomidate, Ketamine, Methohexital

• Propofol (Diprivan) the concentration is 10 mg/ml, and the dose is 1-2.5 mg/kg for 30-60 sec, 5-10 min, always wear gloves
• Etomidate (Amidate) concentration is 2 mg/ml; dose at 0.2-0.4 mg/kg for 30-60 sec, 5-15 min
• Methohexital (Brevital) the concentration is 10 mg/ml; dose at 1-2 mg/kg *ECT
• Ketamine (Ketalar) must have a concentration of 10 mg/ml.
• Ketamine can administered by a 1-2 mg/kg dose for 30-60 secs or more; for 15 min.
• Ketamine can be delivered via IM or oral route, IM – 4 to 6 mg/kg; 2-4 mins or longer.
• Via the oral route give 10 mg/kg; over 10-20 minutes (variable).

Propofol - Various Effects

• Decreased SVR, decreased preload, and decreased myocardial contractility.
• Significant hypotension is possible with propofol.
• Transient respiratory depression, more prominent than that seen with etomidate, is common with induction doses.
• Decreases in tidal volume are greater than decreases in respiratory rate.
• Myoclonia induced by propofol results in spontaneous excitatory movements secondary to selective disinhibition of subcortical centers.
• Hiccups and opisthotonus can result from Propofol administration.

Etomidate - Various Effects

• An alternative to propofol with little if any cardiorespiratory effects.
• Side effects can include pain on injection, hiccups myoclonia, nausea, vomiting, and adrenocortical suppression.
• Etomidate does NOT block SNS response to laryngoscopy.
• Minute volume decreases, but respiratory rate increases; possibility of brief apnea
• Excitatory phenomenon – sudden and often severe muscle movements and tremors, referred to as myoclonia (Incidence 10-60%).
• Etomidate can increase epileptiform activity and possibly increase the risk of seizure for patients that have a history of seizures.

Ketamine - Various Effects

• Ketamine is useful for anesthesia/sedation in high-risk, pediatric, and asthmatic patients.
• Ketamine has excellent analgesic properties.
• Cataleptic: the eyes remain open, the pupils are reactive to light, the corneal reflexes are intact, and horizontal nystagmus is present.
• Lacrimation and eye blinking continues, salivary gland secretions are increased when using Ketamine
• Also, tracheal, bronchial, and salivary muscle gland secretions are increased, which may require antisialagogue use.
• Ventilation is generally preserved, as is normal respirations and intact airway reflexes with Ketamine use.
• Ketamine is the only active bronchodilating induction agent and agent of choice in a patient with active asthma who requires surgery.
• Skeletal muscle tone is increased, and occasional purposeless movements occur that are unrelated to painful stimuli when using ketamine

Induction Doses of Common Anesthetics

• Etomidate: 0.2-0.3 mg/kg
• Propofol: 1-2 mg/kg, or 2-4 mg/kg IV; 4-6 mg/kg IM; 10 mg/kg Oral
• Ketamine: See Box 9.4
• Dexmedetomidine: 1 mcg/kg infused over 10 minutes followed by 0.2-0.7 mcg/kg per hour
• Midazolam: 0.1-0.2 mg/kg

Muscle Relaxants - Succinylcholine and Rocuronium

• Succinylcholine (Anectine) with a concentration of 20 mg/ml.
• Succinylcholine can be administered 1-1.5 mg/kg without pretreatment or 1.5-2 mg/kg with pretreatment.
• IM – delivers 3-4 mg/kg of Succinylcholine.
• Rocuronium (Zemuron) with a concentration of 10 mg/ml.
• Intubation dose is 0.6-1 mg/kg of Rocuronium, up to 1.2 mg/kg.
• Cisatracurium (Nimbex) for patients with renal disease, the Hoffman elimination.
• Cisatracurium contains a concentration: 2 mg/ml.
• Cisatracurium intubating dose is 0.1-0.2 mg/kg.
• Vecuronium (Norcuron) at 0.1 mg/kg.

Muscle Relaxant Tidbits

• Muscle Relaxant allergies primarily follow initial dosing but can occur during emergence with Sugammadex.
• IgE-mediated pathological mechanisms can result from muscle relaxant allergies.
• Succinylcholine and Rocuronium are the most frequently NMBAs involved, while Pancuronium and Cisatracurium are the least. -SMR's are the #1 offending agent when it comes to muscle relaxant allergies.
• Antibiotics are #2 and latex is #3, but can often switch.

Neuromuscular Blocking Agents: Dose, Onset, and Duration

• All data is for adult patients without significant disease.

Side Effects of Succinylcholine

Pretreatment and Priming

• Pretreat with small doses of nondepolarizing muscle relaxants (10-30%) to reduce fasciculations after Succinylcholine administration.
• Pretreat with Zemuron 0.04 mg/kg to decrease incidence of fasciculations and myalgia.
• 5 to 10 mg of Zemuron with Propofol works
• Accelerate the onset of Zemuron when intubating during RSI when administering, use priming.
• Priming involves giving 10% of the calculated intubating dose while inducing anesthesia.
• If respiratory depression develops, or the patient is distressed/anxious reduce to 10%.

Neostigmine and Glycopyrrolate

• Neostigmine (Bloxiverz) is an anticholinesterase that breaks down Ach.
• The commonly available concentration is 1 mg/ml but others exist, so be vigilant!
• The dose must be 0.04-0.07 mg/kg to a maximum dose of 5 mg.
• Neostigmine must be preceded by or given with an anticholinergic medication.
• Glycopyrrolate (Robinul) is an anticholinergic and must precede or be given with neostigmine when using it.
• Glycopyrrolate concentration: 0.2 mg/ml.
• Glycopyrrolate Dose: 0.01-0.02 mm/kg.

DUMBBELLS – Reasons for giving Robinul with Neostigmine

Commonly Used Anticholinesterase, Anticholinergic, and Select Relaxant Binding Agents

TOF Reversal Strategies

Sugammadex (Age 2 and Up)

• The Sugammadex dosage varies from 2 to 16 mg/kg according to the blockade depth during reversal.
• Use twitch responses to determine the timing and dose for Sugammadex.
• For spontaneous recovery that has reached the second twitch during TOF stimulation, give 2 mg/kg.
• For spontaneous recovery that has reached 1 to 2 PTC, administer no twitch responses to TOF stimulation, use 4 mg/kg.
• In patients for whom a clinical need to reverse neuromuscular blockade quickly occurs (failed intubation?) consider 16 mg/kg.
• Limit to 24-hours before Zemuron can be administered again!

Sugammadex Cautions

• Avoid Sugammadex in patients with significant renal disease due to dependence on renal elimination.
• Interactacts with contraceptives and interferes with them, patients using hormonal contraceptives require a nonhormonal method for the next 7 days following administration.

IV Acetaminophen (Ofirmev)

• Administer 1 gram as early as possible, infused over 15 min with a 100 ml bottle or bag and is more impactful in shorter cases.
• Adults > 50 kg dose a max 4 gram/day and no more often than every 6 hours unless less than 50 kg? In that case use 15 mg/kg.
• High cost may preclude routine use.
• Comparison to oral preparations should be kept in mind.
• Look at the label, the presence of Mannitol – can cause transient hTN?

Ketorolac (Toradol)

• Very effective for mild to moderate pain.
• Use must be avoided in patients with atopic or asthmatic conditions, and should use caution in the elderly, or in patients with renal & GI dysfunction, also note the propensity for bleeding disorders.
• Bone healing delayed by NSAIDs leads many clinicians not to use them as analgesics in orthopedic procedures.
• Use 30 mg on patients less than 65 y.o and a normal functioning kidney; otherwise give 15 mg on patients greater than 65 y.o with functioning kidney.
• Can dose 0.5 mg/kg up to 30 mg total.

Other Medications: Lidocaine, Ondansetron & Dexamethasone

• Lidocaine (Xylocaine) at a concentration: 1 or 2% and the dose is 1 mg/kg.
• Ondansetron (Zofran) has a concentration of 2 mg/ml and dose of 4-8 mg.
• Dexamethasone (Decadron)concentration of 4 mg/ml with a dose of 4-8 mg.

Common Drugs for Postoperative Vomiting

• Ondansetron (Zofran): Administer 4-8 mg IV.
• Droperidol (Inapsine): Administer 0.625–1.25 mg IV.
• Haloperidol (Haldol): Administer 1-2 mg IV.
• Metoclopramide (Reglan): Administer 10–20 mg IV.
• Promethazine (Phenergan): Administer 12.5-25 mg IV, note the risk of sedation!
• Dexamethasone (Decadron): Administer Adult 4-8 mg IV, or Child 150 mcg/kg up to 8 mg
• Aprepitant (Emend): Administer 40 mg PO, contraceptive is ineffective for ~ 1 month.

Receptors and Ligands

Induction Tactics

• The goal of Rapid Sequence Induction (RSI) is to minimize time between onset of unconsciousness and tracheal intubation, also reduce the regurgitation risk by applying pressure to the cricoid.
• Though ventilation via a mask is generally avoided in RSI, the use of positive pressure less than 20 cm H2O (called modified RSI) should minimize gastric insufflation risk (if patient develops hypoxemia prior to tracheal intubation).

RSI Tactics

• During a Rapid Sequence Evaluation: confirm the presence of Preanesthesia.
• Always confirm “Anesthesia/In OR Time” has started, Stretcher has been switched to OR Bed.
• Hook up & turn on Monitors and confirm Preoxygenation of a patient, then use Suction | Time Out.
• Administer drugs for Induction + or - Fentanyl, Lidocaine, Propofol, + or - Zemuron
• Confirm a the presence or absence of Eye reflexes, or tape Eye closed.
• Intubate using TOF or secure airway with LMA.
• Secure airway, Ventilator (Controlled vs. Manual)
• Turn Anesthesia On – TIVA or Gas (O2/N20/Gas) (Zofran, Decadron, Ofirmev, Toradol, Precedex, ...

Discharge Considerations

• Always determine whether emergence exists, or if the procedures are still ongoing.
• Chart it or it didn't happen OR it wasn't removed.
• Determine or establish if Reversal of TOF is required.
• Use Controlled > manual > assisted > spontaneous
• Determine if a Deep vs. awake extubation process applies
• Determine a Turnover Time, aim for less than 20 minutes.
• Repeat the observation processs.

Induction Considerations

• Use Anxiolysis methods during induction, with Music, imagery, or benzodiazepines.
• Apply Preoxygenation during induction and denitrogenation (maximize oxygen in FRC).
• Use 100% oxygen for 8 vital capacity breaths over 60 seconds.
• Use 100% oxygen for 3 mins.
• Adapt Pediatric (some adults too) patients and IVs (Mask induction with O2/N2O/Sevo).
• Account for Difficult airways (can maintain spontaneous respirations).
• Perform Priming, by starting/filling the circuit first.
• Note that IV induction, is generally the most common technique used with adults.

Induction of Anesthesia and Methods of Care

• General TIVA (NC to ETT)
• General Mask (IV, No IV w/Gas only)
• General LMA (TIVA or Gas) Methods of Care
• Monitored Anesthsia
• Regional MAC
• Regional General