Credentialing Criteria for Privileges to Administer Sedation/Analgesia by the Non-Anesthesiologist

Transcription

1 Credentialing Criteria for Privileges to Administer Sedation/Analgesia by the Non-Anesthesiologist General Description Medical Staff Policy & Procedure - Ocean Medical Center Purpose: Scope: Policy: To assure a consistent level of care related to minimal to moderate sedation/ analgesia throughout the institution of OMC. OMC Physician/Dental Staff The Chair of the Department of Anesthesia directs this program. The program's Policy and Procedure is attached. I. Credentialing criteria for privileges to administer minimal to moderate sedation/analgesia by the non-anesthesiologist II. The policy for privileges to administer minimal to moderate sedation/ analagesia by the nonanesthesiologist and the care of patients receiving minimal to moderate sedation/analgesia by the non-anesthesiologist DIDACTIC SECTION FOR INFORMATION ONLY: The management of respiratory insufficiency secondary to drug use Clinical pharmacology of useful drugs for sedation/analgesia for the non-anesthesiologist Adult and pediatric testing for certification attached I. Credentialing Criteria for Privileges to Administer Minimal to Moderate Sedation/Analgesia by the Non-Anesthesiologist PURPOSE: Anesthesiologists possess specific expertise in the pharmacology, physiology, and clinical management of patients receiving sedation and analgesia. For this reason the Department of Anesthesiology at OMC has be called upon for the development of the institutional policies and procedures for sedation and analgesia for diagnostic and therapeutic procedures. The purpose of these policies are to allow the non-anesthesiologist clinician under the direction of the Department of Anesthesiology to provide their patients with the benefits of minimal to moderate sedation/ analgesia while minimizing the associated risks. 2 CREDENTIAL CRITERIA: In order for a physician to be granted privileges for the administration of sedation/analgesia, the following criteria must be met: 1. Any physician appointed to the Medical Staff after January 1, 1993 will need residency or fellowship training that includes experience in administration and management of

2 sedation/analgesia documented by his/ her Program Director. Physicians who were on staff prior to January 1, 1993 will provide a letter stating that they have successfully managed twenty (20) cases. It is the responsibility of each Department Director to attest to the applicant's competency in case management. 2. Knowledge of pharmacology of drugs administered, principles of pulse oximetry and management of untoward sequelae of the procedure and agents used. Relevant information will be provided by the Department of Anesthesiology. Successful completion of written examination is required. 3. A minimum of five (5) cases per year will be required to maintain proficiency in the administration of sedation/analgesia. At the time of reappointment, physicians reapplying for this privilege must provide documentation of ten (10) cases performed over the most recent two-year period. A letter should be sent from the Department Director to the Director of the Department of Anesthesiology attesting physician reappointment. 4. All physicians using the technique sedation/analgesia must be certified in Basic Life Support and ACLS and/ or ATLS. Pediatric Basic Life Support and PALS is required for physicians treating pediatric patients. Exception: The State Department of Health in New Jersey has recognized that board certified Emergency Physicians no longer need to achieve ACLS, ATLS, etc. therefore, Emergency Physicians and are exempt from this requirement in this policy. II. The Policy for Privileges to Administer Minimal to Moderate Sedation/Analgesia by the Non-Anesthesiologist and The Care of Patient's Receiving Minimal to Moderate Sedation/Analgesia by the Non-Anesthesiologist DEFINITION: "Sedation and analgesia" comprise a continuum of states ranging from minimal sedation anxiolysis through general anesthesia. The American Society of Anesthesiologists (ASA) has defined four levels of sedation/ analgesia and anesthesia. They are as follows: Minimal sedation (anxiolysis) is a drug induced state during which patients respond to verbal commands. Although cognitive function and coordination may be impaired, ventilatory and cardiovascular functions are unaffected. Light sedation occurs following the administration of medication for reduction of anxiety or pain and allows the patient to maintain normal respiration, eye movement and protective reflexes. Minimal sedation may be provided by the non-anesthesiologist physician approved to give minimal to moderate sedation/analgesia. Moderate sedation/analgesia ("conscious sedation") is a drug induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. No interventions are required to maintain a patent airway, and spontaneous ventilation is adequate. Cardiovascular function is usually maintained. Moderate sedation may be provided by the non-anesthesiologist physician approved to give minimal to moderate sedation/analgesia. Deep sedation/analgesia is a drug induced depression of consciousness during which patients cannot be easily aroused but respond purposefully following repeated or painful stimulation. The ability to independently maintain ventilatory function maybe impaired.

3 Patients may require assistance in maintaining a patent airway and spontaneous ventilation maybe inadequate. Cardiovascular function is usually maintained. Deep sedation is restricted to use by an anesthesia provider. Anesthesia consists of general anesthesia and spinal or major regional anesthesia. It does not include local anesthesia. It is a drug induced loss of consciousness during which patients are not aroused even by painful stimulation. The ability to independently maintain ventilatory function is often impaired. Patients often require assistance in maintaining a patent airway, and positive ventilation may be required because of depressed spontaneous ventilation or drug-induced depression of neuromuscular function. Cardiovascular function may be impaired. Anesthesia is restricted to use by an anesthesia provider. The American Society of Anesthesiologists has published practice guidelines for Sedation/ Analgesia by non-anesthesiologists. All practitioners applying for such privileges should be familiar with these guidelines.3 The American Academy of Pediatrics has published practice guidelines for monitoring and management of pediatric patients undergoing sedation for procedures. Physicians providing sedation/analgesia for pediatric patients should be familiar with these guidelines.4 This policy will be applied when the non-anesthesiology physician/dentist administering or directing the administration of minimal to moderate sedation/analgesia: 1. Has a clinical appointment in a department other than the Department of Anesthesiology. 2. Is administering minimal to moderate sedation/analgesia to a patient undergoing surgery and/or invasive procedure, including, but not limited to, percutaneous aspiration and biopsy, cardiac and vascular catheterization, endoscopy, reconstructions, angioplasty, implantations, and reduction of fractures or dislocation-when the patient is not being ventilated mechanically. 3. Is administering minimal to moderate sedation/analgesia to a pediatric patient during EEG, CAT Scan, MRI or other diagnostic procedures requiring sedation/analgesia. (During MRI, ECG must be used with caution due to risk of thermal injury). N.B. Oral and rectal preparations are often used to sedate patients for no painful procedures such as EEG and radiologic studies. Drugs administered by these routes may produce a state of conscious or deep sedation and have the potential to cause respiratory depression. Patients who receive sedative medications require monitoring until fully alert regardless of the route of administration. Minimal monitoring must include BP, ECG, pulse oximetry and level of consciousness documented every five minutes. This policy will not be applied when nitrous oxide 50% or less is used with oxygen to an otherwise healthy ASA I or II patient and verbal communication is maintained throughout the procedure and documented. Pulse oximeter is not required but recommended in this sub set of patients. A. PURPOSE: The purposes of this document are: 1. To describe the procedure to obtain privileges to administer sedation/analgesia by the non-anesthesiologist at Ocean Medical Center.

4 2. To describe guidelines for the evaluation and care of patients receiving sedation/analgesia. 3. To apply this policy uniformly to all adult and pediatric patients receiving sedation/analgesia at Ocean Medical Center. 4. To provide guidelines for appropriate medications to be used by the nonanesthesiologist. (See attachment: Policy and Procedure for the Clinical Pharmacology of Useful Drugs for Sedation/Analgesia). B. Physicians who want privileges to administer sedation/analgesia will need the approval of their Department Chair and the Chair of Anesthesiology. Request for sedation/analgesia privileges should be submitted to the applicant's Department Chair with a copy to the Chair of Anesthesiology. C. Privileges to administer sedation/analgesia will be recommended by the Chair of Anesthesiology and the Chair of the requesting physician's Department to the Chief of Staff and the Medical Executive Committee for approval by the Hospital Board of Trustees. Elements to be considered are previous education, training, experience, knowledge of the pharmacology of drugs administered, and ability to manage untoward sequelae of the procedure and agents used-especially vagal reactions, hypotension and apnea. This can be determined by: 1. The successful completion of written examination, and 2. Practical evaluation of the patient with the documentation of the established ASA level (definition under Part E. of this Policy), patient history, and patient condition evaluated immediately prior tot the administration of sedation/analgesia medication. 3. The physician will be observed a minimum of three cases by the Chair of their Department or assigned representative to complete the credentialing criteria. (See Section I: Credentialing Criteria for Privileges to Administer Sedation/Analgesia). D. The sedation plan, care and well being of patients receiving sedation /analgesia will be the responsibility of the physician administering the sedation/analgesia who must be continuously present during the procedure. 1. Sufficient number of qualified staff is required to monitor and recover the patient receiving sedation and/or anesthesia. 2. The anticipated needs of the patient are assessed to plan for post-procedure care. 3. Preprocedural education, treatments and services are provided according to the plan of care. E. Care of the Patients: Pre-procedure 1. Patients should be determined to be an appropriate candidate for sedation and analgesia by the use of the ASA physical guidelines and score. ASA 1 = A normally healthy patient. ASA 2 = A patient with mild systemic disease. ASA 3 = A patient with sever systemic disease that limits activity but is not incapacitating. ASA 4 = A patient with severe systemic disease that is a constant threat to life. ASA 5 = A morbid patient who is not expected to survive with or without

5 the operation. ASA 6 = A patient is declared brain dead on life support for organ donation. Patients of ASA Status 4 or greater require mandatory anesthesiology consultation. All patients with airway assessment issues require mandatory anesthesiology consultation. Respiratory Therapy is available for emergency intubation twenty-four (24) hours per day at OMC and an anesthesiologist is on call twenty-four (24) hours per day.. Cath Lab Exception: It may be necessary for the invasive cardiologist to treat patients in the Cath Lab who are ASA Status 3 or greater due to their cardiac disease. This exception has been recognized by the Department of Health in the State of New Jersey. 2. Pre-sedation preparation/ documentation for all Patients: a. Standard fasting orders before elective sedation/analgesia: Adults-four (4) hours NPO (up to 8 oz. Of water may be taken up to two (2) hours before the procedure to facilitate administration of medication). Children-may take water or clear liquids up to two (2) hours before the procedure-then NPO. Infants may take breast milk up to four (4) hours before the procedure. Infant formula may be given to a child up to six (6) hours before a procedure. b. Pre-procedural fasting for the emergency patient: The use of sedation must be preceded by an evaluation of food and fluid intake. When protective airway reflexes are lost, gastric contents may be regurgitated into the airway. Therefore, patients with a history of recent oral intake with other known risk factors, such as trauma deceased level of consciousness, extreme obesity, pregnancy, or bowel motility or function, require careful evaluation before administration of sedatives. If possible, such patients may benefit from delaying the procedure and administering appropriate pharmacologic treatment to reduce gastric volume and increase gastric ph. When pre-fasting has not been assured, the increased risks of sedation must be carefully weighed against its benefits, and the lightest effective sedation should be used. An emergency patient may require protection of the airway before sedation. c. Documentation of the patient's History and Physical examination: With review of systems, current medications and drug allergies prior to sedation/analgesia is required. Some patients with chronic or severe systemic illness, or premature infants less than 48 weeks past conceptual age, or with a history of apnea may not be suitable candidates for sedation/ analgesia. Anesthesiology Department involvement should be considered. Attention should be paid to any anatomic airway abnormality that may be a potential cause of airway obstruction, including tonsillar and adenoidal hypertrophy. d. Laboratory studies or diagnostic screens in areas indicated by the patient's past medical history and present illness: The Department of Anesthesia at OMC requires that all menstruating women should receive a pregnancy test prior to sedation/analgesia. No other routine diagnostic or laboratory tests are required. These requirements must be considered prior to sedation of any patient.

6 e. An accurate, valid consent for the procedure that includes an explanation of sedation/analgesia, other risks and options. f. The patient's status will be re-evaluated immediately prior to the procedure. g. A registered nurse with sedation certification supervises perioperative care. h. See Administrative Policy: Patient Safety Policy: Surgical and other procedure correct patient and site identification and verification policy. i. The following agents and equipment will be immediately available: Procedure 1. An oxygen source, ambu bag, laryngoscope, endotracheal tubes (sizes 5.0mm, 6.0mm, 7.0, 8.0mm), oral and nasal airways, defibrillator, code cart, emergency resuscitative drugs, including Flumazinal and Narcan or Nalmefene. 2. Endotracheal tube size for children older that 1 year may be estimated by the formulate 16 + age (years)/4. Tubes 0.5mm smaller and 0.5mm larger than calculated should be available. 3. Care during the procedure a. Patients must be monitored. The monitoring must be documented on an appropriate record that remains with the patient's chart. Vital signs (blood pressure, pulse, respiration) will be taken at least every five minutes and charted. ECG will be monitored-the rhythm should be noted and charted every five minutes or more frequently as needed. Oxygen saturation will be monitored, documented and charted every five minutes or more frequently as needed. Level of consciousness should be monitored and charted every five minutes or more frequently as needed. b. Supplemental oxygen should be administered to all patients receiving sedation/analgesia. If not used routinely, supplemental oxygen must be added if oxygen saturation drops to 92% or less. c. The route, time and dosage will be recorded on all drugs administered. d. If a patient demonstrates persistent oxygen desaturation (SaO2 less than 90%) despite the use of supplemental oxygen or requires airway support, the case should be terminated unless an anesthesiologist and/or anesthesiologistsupervised nurse anesthetist is available to provide monitored anesthesia care. e. There must be IV access or immediate availability of IV access for all procedures done with PO or rectally administered agents, i.e., ECG, CT Scan, MRI, etc.

7 f. Patients who exhibit hemodynamic instability, oxygen desaturation or respiratory depression/failure are not appropriate candidates for sedation/ analgesia unless monitored anesthesia care (MAC) can be provided or the procedure is done in the ICU or CCU. Arrangements for MAC should be made as early as possible through the Operating Room Booking Office. g. The physician/dentist must administer the first dose of sedation/analgesia when intravenous agents are used (Cath Lab and Interventional Radiology exception noted below), and be present for the titration administration by a conscious sedation certified registered nurse. N.B. Cath Lab and Interventional Radiology Exception: In the Cath Lab due to the sterile presentation of the operating physician, the initial dose may be administered by a certified conscious sedation registered nurse. h. When non-iv agents are used for diagnostic procedures the physician/dentist prescribing the sedative dose of medication must be certified in sedation/analgesia at Ocean Medical Center. The medication must be administered by an appropriate certified practitioner (nurse and/or resident physician) who will remain in constant attendance with the patient until discharge to PACU environment. A competent Registered Nurse must remain present with the patient until appropriate discharge criteria are met. i. Anxiolysis/Relaxation Medication Use in Pediatrics. Anxiolysis or minimal sedation medications such as Chloral Hydrate or other ordered medications given by oral route or by rectal suppository may be administered to the pediatric patient arriving in an ambulatory day stay unit at OMC by order of the physician to provide preprocedure relaxation and anxiety reduction in accepted drug dose range. Anxiolysis is utilized to provide relaxation and lessen anxiety and is not given in dosage to provide analgesia. The administered dosage of the ordered medication should be reflective of that goal or referred to the Department of Anesthesia for evaluation. However, these patients require monitoring continuously through out this process per requirements of this policy Anxiolysis/Relaxation Guidelines: 1. The Physician or Pediatrician ordering the procedure (EEG, CT, MRI) order the prescribed oral medication to be given for an anxiolysis/relaxation effect on the child. -No orders are accepted form non-staff physicians. -All medication orders are by mg/kg formula. -All medication orders must be in total milligrams per dose (as in 50 mg) not in volume dose (as is 1/2 teaspoonful). This is to prevent medication error caused by different pharmaceutical concentration levels of medication available. 2. The patient must have a completed H&P by the ordering physician and a signed hospital consent by the parent or legal guardian. 3. No IV is required for the purpose of administration of oral medication for anxiolysis/relaxation.

8 4. Preprocedure fasting is required. Children must be NPO for four hours prior to the administration of medication. Children may take water or clear liquids up to two hours before the procedure. 5. Prior to the procedure baseline vital signs and minimal monitoring must be provided and documented including level of consciousness, heart rate, blood pressure, respiratory rate, oxygen saturation and temperature. Continuous monitoring is required throughout the procedure per policy. 6. Emergency equipment must be available in the unit for use if needed. 7. Medication is given by Physician or Registered Nurse. The child receives direct observation by PALS certified nurse. 8. The Department of Anesthesiology is available 24 hours per day to provide Anesthesiology services. All questions should be referred to Anesthesiology for clarification or intervention. 9. The time and condition of the child at discharge shall be documented including the child's vital signs and level of consciousness reflecting that the child has returned to a state that is safe for discharge and meets the discharge criteria by the Aldretti score. j. Exception: Analgesia for Urgent Therapeutic Intervention in the Critically Ill Patient. There are circumstances when the critical care physician may need to sedate a patient beyond "anxiolysis/ minimal "light" sedation to perform an urgently needed therapy. Some examples would be, but not limited to: Urgent endotracheal intubation. All painful procedures on the intubated and appropriately monitored critically ill patients. Pediatric critically ill non-intubated patients in the Pediatric Intensive Care Unit. Emergent therapeutic interventions performed in the Emergency Department by appropriately credentialed physicians. k. Exception: Ketamine Use by Non-Anesthesiologists Purpose: To present possible exceptions to the use of Ketamine by the nonanesthesiologist critical physician. It is the belief of the Department of Anesthesiology that as a general rule Ketamine, a potent psychotropic anesthetic, should be reserved for use by members of the Department of Anesthesiology only. There are multitudes of other acceptable sedating medications currently available to achieve the same effect with proper dosing. However, if the non-anesthesiologist critical care specialist needs to perform an urgent therapeutic intervention such as, but not limited to: Urgent endotracheal intubation or therapies on intubated and appropriately monitored critically ill patients, a deeper level of consciousness may be required. In the Pediatric ICU, the pediatric intensivist after appropriate credentialing may choose to use Ketamine in certain circumstances, for therapeutic and/or diagnostic interventions on the non-intubated critically

9 ill pediatric patient. Whenever non-anesthesiologists provide this level of sedation in such previously described conditions, all doses must be given and monitored by the MD personally. The Department of Anesthesiology is available 24 hours per day to provide anesthesiology services. It is required in this institution that a member of the Department of Anesthesiology be consulted for all procedures requiring a deeper level of consciousness than allowed by the Hospital-wide sedation and analgesia policy except in the aforementioned circumstances. l. Exception: Administration of Propofol to the Pediatric Patient in Pediatric ICU by the Pediatric Intensivist. This may not be in violation of this policy providing the following criteria are met: The statement in the AANA-ASA Joint Statement Regarding Propofol Administration, dated April 14th, 2004 reads: "Whenever propofol is used for sedation/analgesia, it should be administered by persons trained in the administration of general anesthesia, who are not simultaneously involved in these surgical or diagnostic procedures. This rustication is concordant with specific language in the propofol package insert, and failure to follow these recommendations could put patients at increased risk of significant injury and death. m. Pain Management Exception for the Administration of Propofol by Registered Nurse with current Conscious Sedation Certification. All Registered Nurses (RN) administering I.V. Conscious Sedation will be I.V. Conscious Sedation Certified as per this policy. All Registered Nurses caring for patient's undergoing procedures for pain management and working directly with an anesthesiologist/pain medicine physician will be permitted to use Propofol (Diprivan) under the direct supervision of the physician. Post-Procedure 5. Post-Procedure Care a. The patient's status is assessed immediately after the procedure and/or anesthesia. b. The patient should go to an appropriate post-anesthesia care area, transported by a physician or a registered nurse. An RN supervises perioperative care. c. Cases where reversal agents Romazicon and/or Narcon are used require at least two (2) hour of monitoring post procedure. d. Monitoring must be continued on all patients, adults and children, until the patient is fully alert, and documentation of the patient's physiological status, mental status, airway patency, pain level and level of consciousness is included in the medical record. Prior to discharge, the patient should be able to talk and sit unassisted (if developmentally appropriate). Very young or disabled

10 children or adults should return to presedation level of alertness and functioning prior to discharge. e. The patient will be discharged from the post-anesthesia recovery area by a physician or by a protocol with explicit criteria, approved by the Medical Executive Committee. f. Outpatients should be accompanied home by a responsible adult. Outpatients are informed not to drive or make important decisions till the next day. 6. Quality Improvement and Outcomes Management The Chair of each Department where physicians in that clinical department administer sedation/analgesia will be responsible for the monitoring and evaluation of the appropriateness of clinical care provided in that Department consistent with current knowledge of anesthesia practice. The Department of Anesthesiology shall be available for consultation upon request. Adverse outcomes associated with the use of sedation/analgesia should be reviewed as a part of the systemic, ongoing Quality Improvement program in each Department where sedation/analgesia is administered. Elements of the Quality Improvement Program will include, but not be limited to, completeness of records, documentation of monitoring and drugs administered, review of patients with Post-Anesthesia Care Unit stay of more than two hours, respiratory arrest, cardiovascular instability and other untoward outcomes, as well as the use of reversal agents such as Romazicon and Narcan. Deaths and/or unexpected intra-operative or post-operative events or outcomes related to sedation/analgesia in any anesthetizing location must be immediately reported to the Chair of the Department of Anesthesiology, who will notify the Division of Health Facilities Evaluation, as required under N.J.A.C.8:43G6.10(c). ATTACHMENT: DIDACTIC SECTION FOR INFORMATION ONLY The Management of Respiratory Insufficiency Secondary to Drug Use In order to appropriately manage patients who are breathing insufficiently following the administration of the anesthetic drugs described, you must first be able to diagnose the problem and then quickly determine the etiology to ensure appropriate management. The signs of respiratory embarrassment are few. In the most full blown scenario you will see apnea, cyanosis and cardiovascular collapse. However, before this stage is reached, there are other clues to impending respiratory distress. These include dyspnea, depression of consciousness, stridor or sonorous breathing, and use an accessory muscles of inspiration.

11 Once it has been determined that the patient is having difficulty breathing, the cause must be determined. Narcotics are the most potent respiratory depressants and are more likely to cause apnea or a decreased respiratory rate than benzodiazepines or barbiturates. However, in high doses or in elderly or debilitated patients, apnea can result form these drugs as well. Probably more common than direct respiratory depression causing apnea or a decreased respiratory rate, the CNS depressants cause respiratory insufficiency by diminishing tone in the muscles of the mandible. The results are partial or complete airway obstruction. In either case, if there is a significant increase in carbon dioxide, it can compound the CNS depressants effects of narcotics, barbiturates and benzodiazepines. In the case of respiratory insufficiency secondary to prolonged effect of succinylcholine, the major effect seen is no respiratory effort at all, or poor respiratory effort with use of accessory muscles of inspiration. This lack of muscle strength is confirmed by asking the patient to lift his head off the table to maintain it for five seconds, or assessing grip strength. Once it is determined that apnea or respiratory insufficiency is the problem, several steps need to be taken, many of which can be done simultaneously. If alone, you should immediately call for help. If the patient has received narcotic, than Naloxone (Narcan) in a dose of mg should be given intravenously. For pediatric dosing: 0.01 to0.1 mg/kg to a maximum dose of 2mg given IV, IM, SQ, or via ETT (Remember that this lasts only 15 to 20 minutes, and subsequent doses may be needed). This may solve the problem, but oxygen should be given as well. If no respirations are detected, then breathing must be done for the patient using CPR or mask with ambu bag. In the event of obstructed breathing, there are several methods for opening the airway. First, there is the head tilt/chin lift maneuver as taught in basic CPR. In this technique one hand is placed on the patient's forehead, tilting the head backward, while the fingers of the other hand are placed beneath the bony portion of the chin, lifting it upward. Second, there is the jaw-thrust maneuver in which the angles of the mandible are gripped with both hands and pulled forward, while at the same time tilting the head backward. Finally, the mandible can be displaced by placing the thumb in the patient's mouth, and the fingers beneath the chin and pulling upward. After opening the airway, you must assess whether there is spontaneous respiration. If the patient is breathing adequately, you only need to maintain a patent airway and administer facemask oxygen. If the patient is breathing spontaneously but inadequately, then you can assist the patient's breathing with a mask and ambu bag. Once the patient initiates a breath, you gently squeeze the bag during mid-inspiration. When finished, you then wait until the patient initiates another breath. When there is no respiratory effort, respiration must be provided completely by mask and bag. If there is difficulty ventilating by bag and mask, placement of an oral or nasal airway may help. If unable to ventilate by mask, the patient should be urgently intubated. In the event that you can ventilate the patient easily but there is no response, and it appears that ventilation will need to be provided for a long time (particularly in the case of a prolonged paralysis from succinylcholine), then the patient should be intubated.

12 Clinical Pharmacology of Useful Drugs For Minimal to Moderate Sedation/Analgesia for the Non-Anesthesiologist BENZODIAZEPINES Chemistry There are two benzodiazepines of particular interest. These are diazepam (Valium) and Midazolam (Versed), both available for p.o. as well as parenteral administration. Midazolam is distinctive in that it contains an imidazole ring structure. Diazepam is very insoluble in water; therefore, its intravenous preparation is a solution of the drug in propylene glycol and benzoic acid. This is extremely irritating, causing pain on injection and occasionally venous scarring. Diazepam is not recommended for I.M. use due to erratic, but predictable, obstruction. Midazolam, on the other hand, because of the imidazole ring, is water soluble at a ph below 4. The preparation of midazolam is the hydrochloride salt buffered to a ph of 3.5. In the body, the ph, and intramolecular rearrangement occurs, changing the physiochemical properties of the molecule, rendering it more lipid soluble. Mechanism of Action The benzodiazepines exert their effects on multiple sites in the CNS. This has been shown to be related to their inability to potentate the actions of the inhibitory neurotransmitter gamma amino butyric acid (GABA). These actions occur at several sites in the CNS including the cerebral cortex, substantial nigra, hippocampus, cerebellum and spinal cord. Biodispostion Diazepam (Valium) It might be expected that diazepam, because of its high lipid solubility, would provide a rapid onset of CNS effects. However, on the contrary, onset of drowsiness and hypnosis is rather slow and irregular. It is not clear whether this is pharmacokinetic or pharmacodynamic effect, or both. Entry into the cerebrospinal fluid is rapid, but its central actions are delayed and of a lesser magnitude than those following the administration of other anesthetics (e.g., barbiturates). This makes diazepam ideal as a premedicant but a poor choice as a drug for the induction for anesthesia. The recover from a single I.V. dose of diazepam is slow, with residual effects detectable for many hours following I.V. administration. Both tissue distribution and redistribution, along with metabolism, play a role in the recovery from a dose of diazepam. Clearance is dependent upon oxidative metabolism in the lover. This results in several pharmacologically active metabolites. One of which is oxazepam, which is marketed as the sedative Serax. It is these active metabolites which contribute to the prolonged duration of CNS effects. This is especially true following repeated doses. Several drugs, including cimetidine have been shown to competitively inhibit oxidative metabolism and thus prolong the action of diazepam.

13 Diazepam has a large volume of distribution and a very low clearance. This results in an elimination half-life of 20 to 40 hours. It is also 98-99% protein bound. Therefore, changes in protein binding, as seen in the elderly or various disease states, can markedly change its elimination half-life. In liver disease, this results in an increase volume of distribution which, in concert with the liver's decreased ability to metabolize drugs, results in a doubling of the elimination half-life. In renal failure, on the other hand, the increase in unbound drugs results in a 2-3-fold increase in hepatic clearance resulting in a decrease in the half-life. Despite these changes in pharmacokinetics, there is only a rough correlation between plasma levels of diazepam and its clinical effects. Up to 20 fold differences in dosage have been seen in patients undergoing similar procedures to produce similar effects. Nonetheless, the dose should be adjusted in the elderly or in patients with liver disease. Midazolam (Versed) Midazolam is much more soluble in aqueous solutions than diazepam. This accounts for the fact that it is much less painful on I.V. or I.M. injection. It is well absorbed after I.M. injection with maximal effects achieved after 15 to 30 minutes. It is extensively metabolized in the liver via oxidative metabolism, then conjugated and excreted in the urine. It is greater that 95% protein bound. The volume of distribution is similar to diazepam; however, clearance is much faster (10 times) due to faster hepatic metabolism. This results in an elimination half-life of 2 to 4 hours. Pharmacologic Actions CNS: Benzodiazepines can produce tranquility, sedation, and in high doses, unconsciousness, because their onset of action is relatively slower than barbiturates. They are much more useful for pre-medication or sedation during procedures than as an induction agent for general anesthesia. In addition, benzodiazepines possess anticonvulsant effects and muscle relaxant properties. The muscle relaxant effect is not due to an action are the neuromuscular junction but rather to effects on polysynaptic reflexes. Their use on muscles is mostly to relax contracted skeletal muscle associated with spasm or joint disease. All benzodiazepines decrease cerebral oxygen consumption and accordingly, cerebral blood flow, although the magnitude is less than barbiturates. CARDIOVASCULAR: In general, benzodiazepines have small effects on the normal cardiovascular system. Typically, there is a slight (approximately 10%) decrease in blood pressure and a minimal increase in heart rate. RESPIRATORY: Several studies have shown the ventilatory response to CO2 is not impaired by benzodiazepines at doses of.075 mg/kg of midazolam or 0.15 mg/kg of diazepam. Nonetheless, if they are given as a rapid intravenous bolus, they can, on occasion, produce transient apnea. Clinical Pharmacology Diazepam

14 Route: This may be given p.o., I.V., or rectally for pre-operative sedation or I.V. for sedation/analgesia during procedures. The I.M. route is painful on injection and is variably absorbed. The onset of the p.o dose is approximately 15 to 20 minutes. Intravenously the onset is much faster (1 to 2 minutes) and, therefore, must be administered with caution, as apnea can occur with rapid injection. Dose: For adults: the dose for p.o. valium is generally 5 to 15 mg p.o. but should be individualized particularly with regard to age and size. Parenterally the dose is anywhere between 2 to 20 mg and should be titrated slowly, looking for clinical effect. I.V. Diazepam is very irritating to veins and can cause phlebitis or venous thrombosis and is painful on injection. For children: mg/kg I.V., p.o. or rectally. It does cross the placenta and, therefore, is not recommended in obstetrics. In peroral endoscopic procedures, increase cough, laryngospasm, and bronchospasm has been reported. Midazolam Route: Midazolam has several advantages over diazepam in that it is water soluble and produces less pain on I.V. injection. Its onset of action and duration are short. Dose: only formulated for I.V. administration, it may be give orally, nasally, I.V., I.M., or rectally. For adults: the dosage I.M. is.07 to.08 mg/kg with 5 mg being the approximate I.V. dose. I.V. dosage for sedation/analgesia should be given slowly over several minutes and titrated to clinical effect. An initial dose of 2 to 3 mg in an average adult is a good starting point, whereas in the elderly or debilitated, 1 to 1.5 mg is appropriate. Generally a total dose of 0.1mg.kg in an average healthy adult is a good guideline, but this is very variable. Rapid administration is associated with significantly more hypotension and respiratory depression than diazepam. For children: mg/kg I.V. given slowly over several minutes and titrated to effect (Max 2.5 mg) mg/kg p.o. (Max.15 mg-onset of action 20-30minutes). 0.3 mg/kg nasally, sublingually, or rectally (onset of action minutes). I.V. preparation has a very bitter taste even when prepared with artificial sweetener and apple juice. Children find sublingual route preferable to nasal route. Erythromycin may significantly prolong its duration of action. It is also not recommended in obstetrics. NARCOTICS Narcotics, as they are used outside of the operating room, are multi-purpose. They are obviously most often used for pain relief. However, they also play an important role as an

15 adjunct in pre-medication and for sedation/analgesia during procedures. There are many currently used narcotics. For the purpose of limiting discussion, this policy will concentrate on Morphine, Demerol, and Fentanyl. General Pharmacology The identification of endogenous, opiate-like compounds (endorphins), followed by the elucidation of specific opiate receptors in the brain and spinal cord, has clarified the understanding of the mechanism of action and pharmacology of narcotics. Multiple types of opiate receptors exist. When opiates bind these receptors, they are able to modify pain pathways. The mu receptor, which is located in high concentrations in the cerebral cortex, thalamic nuclei, the peri-aqueductal gray matter and the spinal cord, mediates the traditional effects associated with narcotics. These include analgesia, respiratory depression, euphoria, and the ability to produce dependence. It is also associated with the side effects of nausea and pruritis. Narcotics which bind the mu receptor include Morphine, Meperidine and Fentanyl. Kappa receptors promote visceral analgesia though not somatic (or epicritic) analgesia. They are associated with sedation and miosis but do not create respiratory depression, nausea or pruritis. The drugs butaphanol (Stadol) and nalbuphine (Nubain) are mixed kappa agonists and mu antagonists. The delta and epsilon receptors are not as well worked out. Nonetheless, as receptors are better understood, narcotics with greater receptor specificity will be able to be developed. Morphine Pharmacokinetics Morphine, like the other intravenous agents discussed already, and like all other narcotics, has pharmacokinetics that are characterized by a biphasic distribution pattern. Although all narcotics bind to proteins to varying degrees, they rapidly distribute out of the bloodstream and localize in tissues such as lung, liver, kidneys and skeletal muscle. Brain concentration is low in comparison to other water soluble, inactive metabolites that are excreted by the kidney. For Morphine, the rapid distribution half-time is 1 to 3 minutes, whereas, its elimination half-time is 4 1/2 hours. Pharmacologic Actions CNS: Morphine produces analgesia, drowsiness, changes in mood and mental confusion. Occasionally, dysphoria will be produced instead of euphoria. Pupillary constriction is characteristic of Morphine, and, in large doses, pinpoint pupils are produced.

16 RESPIRATORY: Morphine is a significant respiratory depressant. Even at therapeutic doses, both respiratory rate and tidal volume are decreased. The response of the brain stem respiratory centers to elevated CO2 is blunted. CARDIOVASCULAR: The major cardiovascular effect of Morphine is vasodilation secondary to dose dependent histamine release. Hypotension can result, particularly in the face of diminished blood volume. There is no significant effect on the heart itself, however, a reflex tachycardia can result from the vasodilation. GI SYSTEM: Hypomotility is the effect of Morphine on the GI tract, whereas the biliary tract responds with spasm and increase pressure in the common bile duct. Dosage and Administration Morphine may be administered p.o., I.V., or I.M. It is well absorbed I.M., but its onset is usually 20 to 30 minutes following injection with its peak effect even later. Intravenously, the peak of respiratory depression occurs soon (in the range of 10 minutes). The usual I.V. or I.M. dose for the purpose of analgesia/sedation is 0.1 to 0.2 mg/kg (Max. 15 mg./dose). The p.o. dose 1.5 to 5 X I.V. dose. Usual starting p.o. dose for adults is mg. Meperidine (Demerol) Meperidine, like Morphine, follows pharmacokinetics characterized by both a rapid and then slower distribution phase. The initial redistribution out of the blood into the vascular tissue beds takes 3 to 5 minutes. The slower distribution phase is 5 to 15 minutes. It is 70% bound to plasma proteins (as opposed to Morphine's 30%), and it volume of distribution is approximately the same as Morphine even though it is more lipid soluble. Meperidine is metabolized in the liver and excreted in the kidney. Unlike Morphine, its metabolites, specifically normeperidine is pharmacologically active. Normeperidine has opoid action and is twice as potent as its parent compound of producing seizures in animals. This fact makes its therapeutic index more than ten times less than Morphine. The elimination half-line for Meperidine is approximately 4 hours, and excretion of metabolites is predominantly via the kidney. The elimination half-life of normeperidine is considerably longer. Therefore, repeated doses, particularly in the face of renal disease, can produce toxicity. Pharmacologic Actions CNS: Therapeutic doses of Meperidine produce CNS effects much like Morphine. These include analgesia, sedation, euphoria, respiratory Depression, nausea and miosis. RESPIRATORY: In equianalgesic doses, Meperidine depresses respiration to the same degree as Morphine. After and IM injection, peak respiratory depression occurs within one hour with a return toward normal in two hours. However, minute ventilation can remain decreased for as long as four hours. CARDIOVASCULAR: The cardiovascular system is affected by generalized vasodilation although the mechanism is not histamine related. There is no myocardial depression associated with Meperidine. When given intravenously it can produce a sinus tachycardia which is sometime pronounced.

17 GI SYSTEM: Meperidine, like Morphine, decreases GI motility. However, on an equianalgesic basis, it causes less spasm in the biliary tract. Though it crosses the placenta and may produce neonatal depression, Meperidine can be cautiously used for obstetrics. Dosage and Administration Meperidine is available as an oral form, but is very poorly absorbed, and not a good choice as an oral analgesic. More commonly, it is administered IM or IV. The onset of an I.M. injection is usually about 10 minutes, with the I.V. rate being roughly 2 to 3 minutes. Either way, its duration of action is shorter than Morphine, usually in the range of 2 to 4 hours. This necessitates more frequent dosing intervals. The usual adult dose is 50 to 100 mg I.M. or 25 to 100 mg I.V. or 1-2mg/kg IV, I.M. or p.o. A dose of 100 mg of Meperidine corresponds roughly to 10 mg of Morphine. The untoward effects of Meperidine are similar to those seen with Morphine and include dizziness, nausea and vomiting, visual disturbances, palpitations and dysphoria. It is noted that the incidence of these side effects is greater in ambulatory patients. In addition, there are specific drug interactions with Meperidine that have serious implications. Severe reactions can occur when Meperidine is given to patients receiving Monoamine oxidase inhibitors. This interaction is characterized by excitation, delirium, hyperpyrexia, convulsions, and severe respiratory depression. Phenothiazines and tricyclic antidepressants react with Meperidine to produce profound respiratory depression which begins later and persists longer that that associated with Meperidine alone. Fentanyl (Sublimaze) Fentanyl is a synthetic narcotic similar in structure to Meperidine. Like the other narcotics, it has a rapid and then slower distribution phase. It is 80% protein bound, but its volume of distribution is similar to Morphine. Likewise, its clearance is similar to Morphine. Nonetheless, clinically it behaves much differently than Morphine and Meperidine. The property that accounts for this is its markedly greater lipid solubility. This creates the rapid onset and shorter duration of action that characterizes its use. Metabolism of Fentanyl is primarily hepatic where it is metabolized to pharmacologically inactive byproducts. These are then excreted in the kidney. Like the other narcotics, its dose should be adjusted in the presence of lover or kidney disease. Pharmacologic Actions The CNS effects of Fentanyl are similar to those of Morphine and Meperidine, i.e., analgesia, sedation euphoria, nausea and vomiting, respiratory depression, miosis and occasional dysphoria. The respiratory depression, though similar in nature to the other narcotics, is potentially more profound in that the onset is so quick. Fentanyl's onset is virtually immediate, and peak depression occurs within 5 to 15 minutes. This generally dissipates after one hour, but the CO2 response curve is still blunted after the analgesic effect is gone. The cardiovascular changes seen in Fentanyl are: No myocardial depression

18 Slight to moderate hypotension secondary to decreased peripheral vascular resistance Sinus bradycardia that is dose related and thought to be centrally mediated. Like Morphine, Fentanyl slows GI motility and produces biliary spasm. Another significant side effect of Fentanyl is muscle rigidity, particularly involving the muscles of the thorax. Though noted with other narcotics, it is much greater with Fentanyl and can make respiration or ventilation very difficult. This phenomenon is generally seen only at higher doses, but to a lesser extent, can be seen with only 1 to 2 ccs. It can be overcome with the use of muscle relaxants, but this is only needed when higher Fentanyl doses are used. Dosage and Administration Although Fentanyl can be administered I.M., it is generally reserved for intravenous use. Given I.V., its onset is effectively instantaneous, and its duration is 30 to 60 minutes. Intramuscularly its onset is approximately 8 minutes, and its duration is 1 to 2 hours. Fentanyl is roughly 100 times as potent as Morphine. Therefore, its standard commercial preparation is in vials where 1 cc equals 50 micrograms. For minor procedures, the recommended dosage is approximately 2 micrograms/kg total dose. This should be carefully titrated to effect and should not be administered unless oxygen, narcotic antagonists, and personnel skilled in airway management are available. (0.5 to 1 microgram/kg per I.V. slowly titrated to effect or maximum dose of 2 micrograms/kg). All patients receiving narcotics will become tolerant to a greater or lesser degree even after short periods of exposure. This must be remembered when giving these drugs, as it can greatly alter the amount needed to produce a given effect. Fentanyl is also available in an oral transmucosal form that is referred to as an oralet or lollipop. The dose is 5-15 microgram/kg. The fentanyl oralet is available in 200, 300, and 400 microgram units. Maximum dose is 400 micrograms regardless of weight. Its use in patients less than 15 kg is contraindicated. Complications include nausea, vomiting, pruritus, and respiratory depression. Fentanyl oralet currently is not recommended at JSMC for sedation/analgesia. Ketamine Ketamine is a phencyclidine derivative that produces dissociative anesthesia characterized by EEG evidence of dissociation between the thalamus and limbic system. Induction of anesthesia is achieved in about 60 seconds after intravenous administration of ketamine (1 to 2 mg/kg) and within 2 to 4 minutes after intramuscular injection (5 to 10 mg/kg). Patients appear to be in cataleptic states in which the eyes remain open with a slow nystagmic gaze. Amnesia is present, and analgesia is intense. Various degrees of hypertonus and purposeful skeleton muscle movements can occur. Skeletal muscle tone helps maintain a patent upper airway, but the presence of protective upper airway reflexes should vomiting or regurgitation occur cannot be assumed. Cardiovascular stimulation due principally to direct stimulation of sympathetic nervous system outflow from the central nervous system by ketamine is useful for induction of anesthesia and