Vanguard Health Management

Vanguard Health Management, Inc.2002 Policy & Procedure

Critical Care Sedation

Critical Care Neuromuscular Blockade –

Protocols

The medications discussed in this document are restricted to ICU/CCU or SICU use under the specified circumstances and require completion of the training program contained in the Conscious Sedation Protocol. This group of protocols does not cover monitored Anesthesia Care (MAC).

This Protocol group is also tied to the Conscious Sedation Protocol for definitions, privileging and testing.

Privileges for Deep Sedation in the critical care settings are restricted to specially trained and credentialed physicians. Generally the only qualifying physicians are: Anesthesiologists, Intensivists, Pulmonologists and Neurologists. Exceptions to this policy can be made on an individual basis for Specialty Surgeons (CV, NS) and Internists with approval by the Medical Executive Committee with documentation of training and experience.

General Information/Purpose:

Appropriate use of sedatives and analgesics can greatly facilitate the care of patients in the ICU by improving rest and relieving suffering.

Appropriate use of paralytics can greatly facilitate mechanical ventilation in these many of these patients

Over-dosing of these agents or selection of an inappropriate agent can result in a prolongation of mechanical ventilation and or the ICU stay, which in turn can result in thousands of dollars of extra costs to the patient.

Accurate knowledge of the onset of action, duration of action, side effects, monitoring, and dosing of these agents is vital to the appropriate use of them.

Sedatives

A. General principles:

1. Use non-pharmacologic measures whenever possible:

a) establish regular sleep-wake cycles

b) minimize stimulation during sleep

c) reassure patient and provide general comfort

d) Use opiates as needed for pain; sedatives are a poor substitute for analgesics when pain is the primary problem facing the patient

2. Identify withdrawal symptoms, which can contribute to agitation

a) narcotics

b) benzodiazapines

c) caffeine

d) nicotine

B. Specific agents:

1. Benzodiazapines:

(I) Lorazepam (Ativan)

(a) general properties:

i) slow onset of action (10-20 minutes)

ii) intermediate half-life (6 hours)

iii) less lipophilic than diazepam and therefore does not accumulate in tissues as much as diazepam and is less likely to exhibit prolonged sedation

iv) no active metabolites

v) elimination not affected by renal or hepatic failure

(b) side effects:

i) respiratory depression

i) good for intermittent bolus administration; can also be used as a drip - especially if prolonged sedation is anticipated

ii) Usual starting dose = 2-4 mg Q 2-4 hours (can go up to 10 mg/hr)

(II) Midazolam (Versed)

(a) general properties:

I) rapid onset of action (usually 2-5 minutes)

ii) relatively short half life ( < 2 hours), however, in critically ill patients, it can accumulate and result in sedation for many hours or even days after discontinuation

(b) side effects:

i) respiratory depression

ii) there is no difference between lorazepam and midazolam in terms of time to awakening after prolonged continuous IV infusion because midazolam accumulates in fat (Crit Care Med 1994; 22:1241-7)

i) Can be used as a continuous drip but it is costly

2. Propofol (Diprivan - Chest 1995; 108:539-48):

a) General properties:

(i) no analgesic properties

(ii) very rapid onset of action (1-2 minutes)

(iii) Very short half-life (10-15 minutes)

b) Side effects:

(i) very lipophilic; requires a dedicated central IV line

(ii) respiratory depression

(iii) bradycardia

(iv) pain at infusion site (central lines preferred)

(v) In high doses, it can result in clinically significant hypertriglyceridemia due to the emulsifying lipids

(c) Care must be taken to avoid accidental contamination of the lipid by unusual infectious organisms (NEJM 1995; 333:147-54)

i) change bottles and tubing Q 12 hours

(ii) may cause a 20-30% fall in systolic blood pressure in some patients

(iii) Use cautiously in patients with increased intracranial pressure

d) Use:

only useful as a continuous infusion

C. Recommendations:

Midazolam should be used for rapid sedation of acutely agitated patients. (Grade of recommendation = C)

Propofol is the preferred sedative when rapid awakening (e.g., for neurologic assessment or extubation) is important. (Grade of recommendation = B)

Midazolam is recommended for short-term use only, as it produces unpredictable awakening and time to extubation when infusions continue longer than 48–72 hours. (Grade of recommendation = A)

Lorazepam is recommended for the sedation of most patients via intermittent i.v. administration or continuous infusion. (Grade of recommendation = B)

The titration of the sedative dose to a defined endpoints recommended with systematic tapering of the dose or daily interruption with retitration to minimize prolonged sedative effects. (Grade of recommendation = A).

Triglyceride concentrations should be monitored after two days of propofol infusion, and total caloric intake from lipids should be included in the nutrition support prescription. (Grade of recommendation = B)

Neuromuscular blocking agents

(Society of Critical Care Medicine: "Practice Parameters For Systemic Intravenous Analgesia And Sedation For Adult Patients In The Intensive Care Unit"; September, 1995)

Four rules should guide the use of paralytics. First, paralytics should always be avoided if management can be achieved with sedatives alone. Second, patients should be monitored carefully for coincident organ failure. Third, dosage and duration of paralytics should be limited. Fourth, daily or twice-daily withdrawals of paralytics should be attempted to determine if they are really needed. It remains to be determined if monitoring with peripheral nerve stimulators will become a standard fifth rule.

A. Site of Action: neuromuscular junction:

1. acetylcholine is produced in nerve terminals by acetylation of choline by choline acetylase

2. nerve impulses cause release of acetylcholine

3. acetylcholine binds to nicotinic cholinergic receptors on muscle

4. depolarizing agents bind to receptor and prevent normal closure of receptor with loss of intracellular potassium

these agents cause fasiculations as the drug initially takes effect
example: succinylcholine

5. non-depolarizing agents block acetylcholine from interacting with the receptor

a) these agents do not cause fasiculations

B. Uses:

facilitating intubation

facilitating ventilation

minimizing increases in intracranial pressure by coughing, suctioning, etc.

treating neuroleptic malignant syndrome & tetanus

C. Precautions

Patients are awake and not sedated by these agents

ALL patients receiving these drugs need concurrent use of sedatives

Lack of sedation may be manifest as unexplained hypertension, tachycardia, or diaphoresis

Use of a daily neuromuscular blocker holiday facilitates assessment of the adequacy of concurrent sedation

Extra caution should be taken to insure that ventilator alarms are always on since the patient is unable to ventilate on their own and can rapidly die if there is an unrecognized ventilator malfunction

All patients treated with these agents require specialized nursing care:

(a) eye lubricant & taping lids shut to prevent corneal ulcers

(b) frequent repositioning to avoid decubitus ulcers and compression neuropathy

(d) Frequent range of motion activities to prevent contractures

Peripheral nerve stimulation is recommended for all patients receiving prolonged paralysis

(a) this is performed by trained therapists using the "train of four" protocol

i) ulnar nerve (use lateral face if hand is edematous)

ii) patients rarely require paralysis associated with less than 2-3 twitches on nerve stimulation

iii) if there are 0 twitches, the patient is over paralyzed

(b) this is only recommended as an adjunct to clinical assessment

i) in general - use the lowest amount of an agent that provides the desired end-point (i.e., facilitating ventilation); this may be associated with a full 4 twitches on train of four assessment but the true end point is the clinical assessment

(ii) titrate to weakness NOT paralysis

(c) patients should be given a "neuromuscular blockade holiday" and the dose held once per day while receiving non-depolarizing blockers to insure that they are not over paralyzed

These agents provide NO sedation and unless patients are concurrently given a sedative (preferably a benzodiazepine with amnestic properties) then they will be paralyzed but completely awake

(a) unexplained tachycardia in the paralyzed patient should be considered as evidence of inadequate sedation

(b) appropriate use of sedatives will generally reduce

the amount of a neuromuscular blocker required for clinical effect by relieving anxiety and causing hypnosis

Prolonged use of non-depolarizing agents will result in proliferation of acetylcholine receptors on the myocyte (similar to neuromuscular disease or stroke) - this can result in massive potassium release if succinylcholine is subsequently used; therefore, if a patient has been receiving non-depolarizing agents, they should NOT subsequently receive succinylcholine

Critical Care Sedation –

Protocol for Propofol (Diprivan)

Indications for Use in the Critical Care Unit

Short-term sedation (24 – 48 hours) in intubated or respiratory-controlled (ventilated) adult ICU patients.

Propofol for ICU/CCU Sedation

Central line administration is preferred due to venous irritation with peripheral administration. A volumetric pump is required.

Propofol injectable emulsion should not be mixed with other therapeutic agents prior to administration.

Propofol injectable emulsion will be prepared for single patient use only.

When propofol injectable emulsion is administered directly from the manufacturer’s vial, the vial rubber stopper will be disinfected using 70% isopropyl alcohol and a sterile vent spike and sterile tubing will be used for administration.

As with other lipid emulsions, the number of intravenous line manipulations should be minimized.

Administration should commence promptly and must be completed within 12 hours after the vial has been spiked when propofol injectable emulsion is administered directly from the manufacturer’s vial.

Produces sedation/hypnosis rapidly (within 40 sec) and smoothly with minimal excitation; decreases systemic vascular resistance; rarely is associated with malignant hyperthermia and histamine release; suppresses cardiac output and respiratory drive; does not impair renal or hepatic function.

If propofol injectable emulsion is transferred to a syringe or other container prior to administration, the handling procedures for general anesthesia/MAC sedation should be followed and the product should be discarded and administration lines changed after 6 hours.

Limitations: Propofol

Propofol should not be infused for longer than 5 days without providing a drug holiday to safely replace estimated or measured urine zinc losses.

In patients who are predisposed to zinc deficiency, such as those with burns, diarrhea, and/or major sepsis, the need for supplemental zinc should be considered during prolonged therapy with Propofol.

In patients at risk for renal impairment, urinalysis and urine sediment should be checked before initiation of sedation and then monitored on alternate days during sedation.

Warnings:

Contraindications

Patients known to be hypersensitive to propofol Injectable Emulsion or its components (soybean oil, egg lecithin, glycerol)
Patients in whom sedation is contraindicated

Not recommended for

Nursing/pregnant patients
Pediatric patients
Patients who are not intubated and mechanically ventilated

Use with caution in

Patients with hyperlipidemia
Patients who are hypotensive, hypovolemic, or hemodynamically unstable
Patients with renal and/or hepatic insufficiency requiring long-term sedation because propofol has not been evaluated in this patient population

THIS AGENT IS NOT FOR PEDIATRIC USE unless ordered and monitored by an anesthesiologist.

Analgesic requirements

Although there are reports of reduced analgesic requirements during administration of propofol, in clinical trials, most patients received opioids for analgesia during maintenance of ICU sedation
Patients should be evaluated for their level of pain and provided with appropriate analgesics. When the pain is adequately controlled, titration of propofol is recommended to achieve the desired level of sedation

Desired Level of Sedation Ordered by Physician (Use Ramsay Sedation Scale)

Establish desired level of sedation ordered by physician in Physician’s Order.

Light sedation Levels 1 to 3;

Deep sedation Levels 4 to 6.

Level

Response

1 / Awake, anxious, and agitated
2 / Awake, cooperative, oriented, and tranquil
3 / Awake, responds to commands only
4 / Asleep, brisk response to stimuli
5 / Asleep, sluggish response
6 / Asleep, no response

Dosage and Titration in the Critical Care Unit - Individualize dosage and rate of infusion

Initiation: Start with 5 mcg/kg/min (0.3 mg/kg/hr) for the first 5 mins

Titration: Increase rate by 5-10 mcg/kg/min (0.2-0.6 mg/kg/hr) over 5 – 10 mins until desired level of sedation is achieved; use lower doses in elderly/debilitated patients

Maintenance Rates: The dose range is 5 – 50 mcg/kg/min (0.3 to 3 mg/kg/hr).

Standard infusion: Propofol 1%, 10mg/ml

Special Handling

Always maintain strict aseptic technique with propofol; change bottle/tubing Q 12 HRS.

Adverse Effects

Apnea; movement hypotonia; hallucinations; neuropathy; Hypotension (26%); bradycardia, decreased cardiac output (>1%); hyperlipidemia (3% - 10%); Respiratory acidosis during weaning (3% to 10%).

Drug interactions/compatibility

Narcotic agents and sedatives may increase the sedative effects of Propofol and may also result in more pronounced decreases in blood pressure and cardiac output

Dose requirements of Propofol throughout sedation may be reduced in patients receiving concomitant narcotic therapy and/or those recovering from anesthesia

Patients not receiving concomitant analgesics may require higher maintenance rates of sedation

No significant adverse interactions with commonly used premedications or drugs used during sedation (including a range of muscle relaxants, inhalational agents, analgesic agents, and local anesthetic agents) have been observed

Propofol should not be premixed with other therapeutic agents

Management of Hypotension

Increase IV fluids to maintain SBP > 90 and decrease rate of Propofol until BP can be stabilized. Notify attending physician immediately if significant problems with blood pressure or cardiac output.

Monitoring

Assessment: Wake up and assessment of CNS function should be carried out DAILY throughout maintenance to determine the minimum dose required for sedation. Document CNS evaluation.

Monitor ventilation and oxygenation status (keep 02 saturations > 90%)
Monitor for signs of hypotension or cardiovascular depression.
Monitor patients at risk of hyperlipidemia for increases in serum triglycerides.

Monitor for signs of over sedation (impaired reflexes, hypotension).

Critical Care Sedation –

Protocol for Midazolam (Versed)

Actions

A short-acting benzodiazepine CNS depressant; depresses all levels of CNS, including limbic and reticular formation.

Indications for Use in the Critical Care Unit

Short-term sedation (24 – 72 hours) in intubated or respiratory-controlled adult ICU patients

Contraindications / Precautions

Hypersensitivity to benzodiazepines; pregnant; uncontrolled pain; existing CNS depression; shock; acute narrow-angle glaucoma; acute alcohol intoxication; coma. DO NOT use if patient requires frequent (e.g., Q1H or Q4H) neurological assessments.

Desired Level of Sedation Ordered by Physician (Use Ramsay Sedation Scale)

Establish desired level of sedation ordered by physician in Physician’s Order.

Light sedation will be Levels 1 to 3; Deep sedation will be levels 4 to 6.

Level

Response

Dosage and Titration – Individualize Dosage and Rate of Infusion

Note: Midazolam is 3 to 4 times as potent per mg as diazepam.

Initiation: To rapidly initiate sedation, use 0.01 to 0.05 mg/kg IV slow push over 2 mins.

Titration: Start with 0.02 mg/kg/hr and titrate up to 0.1 mg/kg/hr (1 – 7 mg/hour). Decrease infusion rate by 10% to 25% every few hours to find the minimum effective infusion rate. The use of an opioid (morphine, etc.) concurrently will result in a reduction in the minimum effective infusion rate.

Maintenance Rates: 1 to 7 mg/hour; may use up to 10 mg/hr in some patients; Use lowest dose possible to achieve desired level of sedation ordered by physician. Reduce doses and infusion rates in elderly/debilitated or chronically ill patients (CHF patients have a 2-fold increase in half-life) or those with renal or hepatic dysfunction.

Standard Drip: Midazolam 50 mg in 50 ml D5W or NS (final concentration: 1mg/ml). Remove an equal amount of D5W or NS from bag equal to volume of midazolam to be added; 24H stability.

Special Handling

Midazolam is a controlled substance. Pharmacy is to prepare infusions; emergency infusions may be prepared by nursing during after-hours only.

Adverse Effects

Apnea; hypotension, bradycardia, or reduced cardiac output; arrhythmias

Monitoring

Assessment: Wake up and assessment of CNS function should be carried out DAILY throughout maintenance to determine the minimum dose required for sedation. Document CNS evaluation.

Monitor ventilation and oxygenation status (keep 02 saturations > 90%);
Monitor for signs of over sedation (impaired reflexes, somnolence, coma, confusion, hypotension).

Critical Care Unit Sedation –

Protocol for Lorazepam (Ativan)

Actions

An intermediate-acting benzodiazepine CNS depressant; depresses all levels of CNS, including limbic and reticular formation. Compared to midazolam, lorazepam is longer acting, causes less hypotension, causes equally effective anterograde amnesia, and with prolonged administration produces more rapid awakening.

Indications for Use in the Critical Care Unit

Preferred agent for the prolonged treatment of anxiety (> 24 – 72 hours) in the critically ill adult.

Contraindications / Precautions

Psychoses, acute narrow-angle glaucoma; hypersensitivity to benzodiazepines; Use with extreme care in elderly, very ill patients or those with limited pulmonary reserve due to possibility of apnea or cardiac arrest. Do not give to patients in shock, coma or those with acute alcohol intoxication. Do not give intra-arterially (causes arteriospasm leading to gangrene).

Desired Level of Sedation Ordered by Physician (Use Ramsay Sedation Scale)

Establish desired level of sedation ordered by physician in Physician’s Order.

Light sedation will be Levels 1 to 3; Deep sedation will be levels 4 to 6.

Level

Response

Dosage and Titration – Individualize Dosage and Rate of Infusion

Initiation: Initial IV bolus of 0.5 - 2mg at a rate not to exceed 2mg/min (use lower doses if elderly or debilitated). Dilute contents of lorazepam in pre-filled syringe or vials with D5W prior to administration.

Titration: May use intermittent doses of 0.5 – 4 mg IV Q 4-6H PRN (use lower doses if elderly or debilitated) to achieve desired level of sedation. For continuous infusion, start with 1mg/hr and titrate by 1mg/hr every hour until achieve desired level of sedation.

Maintenance Rates: Usual maintenance rates are 1 – 4 mg/hr.

Standard Drip: Lorazepam 50mg in 50 mL D5W (MUST USE GLASS CONTAINER and In-Line FILTER). Remove an equal amount of D5W from IV bag that corresponds to volume of Lorazepam to be added. 24 H Stability.

Special Handling