University of Kentucky Medical College of Georgia THE USE OF ANALGESICS, SEDATIVE MEDICATIONS AND MUSCLE RELAXANTS IN CHILDREN CHERI LANDERS, M.D. University of Kentucky LYNNE W. COULE, M.D. Medical College of Georgia

Why sedate a child? improve patient tolerance of procedures, invasive monitors and unfamiliar environments airway control decrease the work of breathing decrease oxygen demand reduce anxiety and pain

Examples Procedures: Radiologic Imaging Bone marrow aspiration Minor surgical procedures PIC/deep line placement Decrease agitation while on mechanical ventilation Facilitate air exchange in severe asthma Decrease oxygen demand in septic shock As an example of the variety of procedures for which children are sedated, I looked back at the procedures that Dr. Werner and I were requested to provide sedation for pediatric sedation service over the past year.

Analgesia/Sedation Myths and Concerns Children don’t feel pain/anxiety like adults Respiratory depression Hemodynamic compromise Addiction

Analgesia/Sedation Myth Children DO feel pain/anxiety Anatomy Myelinated and unmyelinated fibers transmit electrical impulse Impulse travels faster when myelinated Psychological

Analgesia/Sedation Concerns Respiratory depression Receptor based phenomenon Need to titrate Caveat in the < 6 month old infant Opioids can cause apnea prior to pain relief

Analgesia/Sedation Concerns “Addiction” Addiction vs. Tolerance vs. Dependance

Addiction A common fear voiced by parents Less common in hospitalized patients than in the general population Includes a psychological “need” or craving along with physical withdrawal symptoms if medication is discontinued

Tolerance The same dose of medication no longer has the same effect as when first started More commonly occurs in patients on long term continuous infusions of sedatives or analgesics rather than intermittent dosing

Dependence Removing medication results in withdrawal symptoms To avoid withdrawal, may need to wean sedative or analgesic when patient has been on the medication for 1 week or more

What is sedation?

Continuum of Consciousness Awake, baseline General anesthesia Conscious sedation Drowsy Deep sedation

Level of Sedation Required In general, the younger the child and the lower their cognitive abilities, the more deeply sedated they will need to be to accomplish the same procedural goal

Conscious Sedation “ A medically controlled state of depressed consciousness that allows reflex ability to maintain a patent airway, and permits appropriate neurological responses to verbal stimuli.”

Deep Sedation “A medically controlled state of depressed consciousness or unconsciousness from which a patient is not easily aroused. It may be accompanied by a loss of protective reflexes and includes an inability to maintain a patent airway and respond appropriately to stimuli”.

Benzodiazepines Bind CNS GABA receptors Skeletal muscle relaxation Amnesia Antegrade and retrograde Anxiolysis Respiratory Depression

Midazolam (Versed) Advantages: anxiolysis, sedation, motion control retrograde amnesia PO, IV, IM, IN, PR dosing routes onset 2-6 min after IV administration, 45-60 min duration available reversal agent Flumazenil

Midazolam (Versed) Disadvantages No analgesia Paradoxical reactions More than additive risk of respiratory compromise when added to opiate Neonates: hypotension and seizures with rapid injection Peak serum level increased with itraconazole, erythromycin and clarithromycin Now, moving on to those commonly used medications that have an analgesic effect that would be used to sedate for a painful procedure.

Barbiturates General CNS depressants Induction of anesthesia Hypnosis Sedation Respiratory depression

Pentobarbital (Nembutal) Advantages: Fairly safe Sedation, motion control, anxiolysis Short onset (3-5 min. given IV) and duration (15-45 min.) Alternative to chloral hydrate in older children PO, IV, IM, PR dosing routes longer time to onset and longer duration with routes other than IV

Pentobarbital Disadvantages Enhances pain perception No reversal agent

Chloral Hydrate Advantages PO, PR dosing initial 25-100 mg/kg repeat after 30 min if need 25-50 mg/kg Anxiolysis, sedation, motion control Single dose toxicity is low Successful in younger patients (< 2-3 yrs) Many practitioners familiar with its use

Chloral Hydrate Disadvantages 15-30 min to onset, lasts 1-2 hours Less successful in older children High doses can cause respiratory depression and dysrhythmias No pain control Not reversible Repetitive doses cause metabolites to accumulate with unknown toxicities Repetitive doses as in those used for insomnia “High doses” mean about 6 times higher than those used for sedation

What is pain? Physical or mental suffering or distress

Two components of pain Physical stimulus Affective response

Analgesia “I can’t think of any other area in medicine in which such an extravagant concern for side effects so drastically limits treatment.” M. Angell. The quality of mercy. NEJM, 1982;306.

What is Analgesia? “Relief of the perception of pain without intentional production of a sedated state. Altered mental status may be a secondary effect of medications administered for this purpose.”

Local analgesia for procedures EMLA Cream Apply to intact skin with occlusive dressing 30-60 min prior to procedure Buffered Lidocaine (1 ml bicarb/9 ml 1% lidocaine) Maximum dose lidocaine 4.5 mg/kg without epinephrine 7 mg/kg with epinephrine

Narcotic Analgesics Activate descending CNS tracts Sedation Analgesia Respiratory depression Moderate anxiolysis

Fentanyl Opioid Advantages analgesia 100x more potent than morphine shorter duration than morphine onset in 2-3 min, lasts 30-60 min less histamine release than morphine available reversal agent naloxone Fentanyl is preferred over other opioids because of its faster onset and shorter recovery period and lack of histamine release.

Fentanyl Disadvantages: no amnesia “Steel chest” or “rigid chest” phenomenon more likely with large bolus dose Treat with reversal of fentanyl or paralyzation Next, ketamine…...

Morphine Opioid Advantages Disadvantages Analgesia Less expensive than fentanyl Disadvantages no amnesia, anxiolysis Histamine release - wheezing, hypotension Longer onset than other opioids

Ketamine Dissociative anesthetic Advantages provides both analgesia and amnesia preserves upper airway tone and reflexes causes bronchodilatation May be the preferred agent when fasting not possible due to UA reflexes maintained. Also a good agent in patients with asthma.

Ketamine Disadvantages increases intracranial pressure laryngospasm hypersecretory response parents disturbed by blank stare emergence phenomenon/agitation

Ketamine Relative contraindications head injury airway abnormalities procedures where posterior pharynx will be stimulated glaucoma, acute globe injury psychosis thyroid disorder

Pre-sedation History General health Risk factors for sedation Current medications Allergies Previous anesthetic reactions patient / patient’s family Why is sedation required? Medications to be used

ASA Physical Status Class I: Healthy patient Class II: Systemic disease Class III: Severe systemic disease Class IV: Severe systemic disease that is a constant threat to life Class V: Moribund / not expected to survive without surgery

In general, consider anesthesia or critical care involvement in patients that are ASA Class III or above and are not in the PICU

Pre-sedation Physical Examination Neurologic exam Airway exam Respiratory status Cardiovascular exam

Personnel Responsibilities Evaluation Monitoring Familiarity with medications Anticipation of side effects Resuscitation

Monitoring General considerations Heart Rate, Respiratory Rate, Blood Pressure Continuous pulse oximetry ECG Perfusion Neurologic status State of consciousness Pupillary responses

Discharge after Sedation for Short Procedure Ability to sit unassisted or flex their neck Verbal responses appropriate for age Protective airway reflexes intact Hemodynamic stability Spontaneous breathing/good oxygenation The patient has returned to their pre-sedation level of function

Neuromuscular Blockade Achieves profound weakness of striated muscle without affecting the function of the cerebral cortex, smooth muscle or the myocardium.

Neuromuscular Blockade NEVER muscle relax a patient without assuring adequate sedation/analgesia beforehand. ALWAYS confirm the patient is easily hand-bag-ventilated prior to paralyzing

Monitoring Muscle Relaxants Progression of weakness: small rapidly moving muscles of the fingers and eyes muscles of the neck, limbs and trunk muscles of respiration Recovery occurs in reverse order; the diaphragm recovers first

Monitoring Muscle Relaxants Nerve stimulators: Stimulate nerve causing contraction of the corresponding muscle Train-of-four monitoring: 1 out of 4 twitches = 90% receptor blockade Fade Absent muscular response

Monitoring Muscle Relaxants Clinical monitoring: Negative inspiratory force Flexion of neck muscles Infants: Hand grasp Grimace Flexion of hips

Muscle Relaxants Cause weakness followed by a flaccid paralysis Depolarizing muscle relaxants Stimulate motor nerve endings Non-depolarizing muscle relaxants Compete at receptor site All cause diaphragmatic paralysis

Muscle Relaxants Depolarizing Agents Imitate the affects of acetylcholine Initial fasciculations followed by paralysis Prevent repolarization of the muscle membrane Quick onset Succinylcholine is the only depolarizing muscle relaxant in clinical use

Succinylcholine – adverse effects Profound bradycardia Hyperkalemia Increased intracranial and ocular pressure Hypersensitivity reactions Muscle pains Malignant hyperthermia Rhabdomyolysis

Succinylcholine Contraindications Patients with paraplegia following strokes or burns muscular dystrophies, myotonia patients with a family history of malignant hyperthermia.

Muscle Relaxants Non-depolarizing Agents Competitively inhibit the binding of acetylcholine Most are steroid based

Pancuronium Non-depolarizing Tachycardia and hypertension due to muscarinic cholinergic blockage Renal elimination

Vecuronium Non-depolarizing No cardiovascular effects More expensive than pancuronium Hepatic elimination

Atracurium and Cisatracurium Non-depolarizing Short duration Best to use as continuous infusion Hofmann elimination Ideal agent in hepatorenal failure

Summary The hospital and especially the PICU are scary places for children. Therefore, the use of anxiolytics and analgesics to facilitate procedures and medical therapies is key to the proper care of the child.

Summary Safe use of sedatives requires knowledge of the medication used as well as close observation and monitoring of the child throughout the period of altered consciousness.

Summary When muscle relaxation is necessary, confirm that the child is adequately sedated and able to be ventilated manually prior to administering a paralyzing agent.