Transfer Guidelines for Malignant Hyperthermia Marilyn Green Larach M.D. Senior Research Associate The North American Malignant Hyperthermia Registry of MHAUS Because successful management of an MH crisis demands fast reactions for successful outcomes, we’ve developed transfer guidelines. Contact me by email at mlarach@gmail.com if you wish an annotated copy of this lecture. Please do not share electronically.

Disclosure Statement Dr. Larach received an MHAUS honorarium To support guideline development Both MHAUS and the ASF sell transfer of care posters No financial benefit to Dr. Larach MHAUS = Malignant Hyperthermia Association of the United States ASF = Ambulatory Surgery Foundation, affiliated with the Ambulatory Surgery Center (ASC) Association

Goals of Talk Introduce Transfer of Care Guidelines Discuss Need for Guidelines Provide Overview of Content Review MH Presentation & Treatment Goals of talk: These are guidelines and not protocols. Also, to share with you clinically relevant results of Registry study concerning MH presentation and treatment. Three references: 2010 Transfer of Care poster, 2008 MH Treatment poster, 2010 Anesthesia and Analgesia Registry publication.

Assumes an ASC using MH Triggers has Available: Anesthesia Care Provider 36 Vials of Dantrolene MHAUS Emergency Therapy Poster MH Crisis Drills Please do not share electronically. Photographic credit for MH drill picture to Outpatient Surgery Magazine (February 2010, p. 30) Credit for Emergency Therapy Poster to MHAUS

Key elements to successful MH treatment: team, MH cart with dantrolene, appropriate monitors Photographic credit to Outpatient Surgery Magazine Online, (Fielder C. Managing malignant hyperthermia. 2010; 9:30)

Actual Transfer of Care Poster--Please do not share electronically.

Development of Guidelines for Emergent MH Transfers Joint Consensus Document ASF MHAUS 13 Panel Members Anesthesiologists CRNA Emergency Medicine Physician Emergency Medical Technician ASC nurse/administrator ASF nurse/administrator Transfers between ASC and Acute Care Hospital 2 year process under the direction of Drs. Sharon Dirksen, Henry Rosenberg, and me. 8 Anesthesiologists included physicians with expertise in MH, pediatric and adult anesthesia, in-patient and ASC anesthesia and a SAMBA representative.

Guideline Goals Assist ASC to prepare own individual emergent MH transfer plan predicated on the facilities and capabilities of the: ASC Emergency transport services Receiving hospital Transfer of Care poster Develop a transfer plan specific for MH that allows for continuation of care for these critically ill patients.

Guidelines and Not Protocol ASC Locations Vary Staff Resources Lab Resources Distance to Receiving Hospital Is your ASC close to or far away from the receiving hospital? Illustration of the variability of ASC’s even within one state. The upper Ambulatory Surgery Center is embedded in a large new outpatient facility of the University of Pennsylvania. The lower ASC is free-standing and located next to a corn field, but it is also less than a mile away from its receiving teaching hospital, Penn State Hershey Medical Center. Photographic credit: Hospital of the University of Pennsylvania and Penn State Hershey Medical Center (Hershey Outpatient Surgery Center)

Guidelines and Not Protocol Emergency Transport Services Vary Availability Weather Distance to Receiving Hospital Severity of Patient Condition Photographic credit for air ambulance: Penn State Hershey Medical Center Photographic credit for ground ambulance: Wikipedia

Guidelines and Not Protocol Receiving Hospitals Vary Facilities Personnel Hospitals come in different sizes with different facilities and services Photographic credit: Wikipedia Commons: University Hospitals of Cleveland Photographic credit: Steve Rasmussen, Rural Roads, Summer 2010 (National Rural Health Association) [Kiowa County Memorial Hospital]

HIPAA allowable What are the first signs of an MH reaction Photography credit to the Post and Courier (Charleston, SC)

Recognition of Suspected MH First signs Hypercarbia Sinus tachycardia Masseter spasm Temperature abnormalities may be early MH sign Most common pattern Respiratory acidosis and muscular abnormalities Increased temperature or rapidly increasing temperature first to third MH sign in 64% of patients with median temperature maximum of 39.1C Respiratory acidotic pattern: inappropriate hypercarbia, tachypnea, ETCO2>55 torr, arterial pCO2>60 torr, or arterial pH<7.25 Muscular pattern: masseter spasm, generalized muscular rigidity, cola-colored urine, peak CK >10,000 U/L or peak K+>6.0 mEq/L MH Clinical Presentation Paper: Larach et al., Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006, Anesth Analg 2010; 100:498 -507

How do we treat an MH crisis? Photographic credit to the Post and Courier (Charleston, SC)

Begin Treatment Declare MH Emergency Discontinue Triggering Agents 100% Oxygen at High Flow Give Dantrolene 2.5 mg/kg IV push Titrate to effect Initiate Transfer Plan Whenever possible, don’t move unless clinician judges patient to be stable Transfer of Care Poster Dantrolene: 36 vials of dantrolene sodium for injection must be available wherever MH trigger agents are used MH Clinical Presentation Paper Data: Dantrolene: Initial dantrolene dose for 229 MH Events was a median of 2.4 (1st quartile 1.9, 3rd quartile 2.8, range 0.01-15.00) mg/kg *Transfer of Care Poster: *If possible, the patient should be moved when, according to the clinician’s judgment, the patient is stable.”

Key Patient Stability Indicators ETCO2 is declining or normal HR is stable or decreasing No ominous dysrhythmias Temperature is declining Generalized muscular rigidity is resolving (if present) IV dantrolene administration has begun Transfer of Care Poster

MH Morbidity and Mortality Consciousness Level Change/Coma Cardiac Dysfunction Pulmonary Edema Renal Dysfunction Disseminated Intravascular Coagulation Hepatic Dysfunction Other Relapse Death MH Clinical Presentation Paper Data: In a Registry study of 181 MH events, 35% of all MH cases had complications including 19% relapse rate (new clinical sign of MH>120 minutes after initial presentation). There were 8 cardiac arrests and 4 deaths. Higher maximum temperatures significantly increase the likelihood of all MH complications including DIC that is associated with a 50-fold increased likelihood of cardiac arrest and and an 89-fold increased likelihood of death

Factors Increasing MH Complication Likelihood Increased time 1st sign to 1st dantrolene For every 30 minute increase in the interval between 1st MH sign and 1st dantrolene dose, the complication likelihood increased 1.6 times. Increased maximal temperature For every 2C increase in maximal temperature, the complication likelihood increased 2.9 times. MH Clinical Presentation Paper Data To avoid MH complications, you need to give dantrolene early and you need to control temperature.

Transport Team Type varies with scenario & transport time Capabilities Ventilatory support Cardiopulmonary & temperature monitoring Fluid resuscitation Medication administration Life support Phone communication May require ASC anesthesia staff Transfer of Care poster Medication administration includes but not limited to: IV dantrolene, non-depolarizing muscle relaxants, sedatives/hypnotics Phone communication: transport command center and MH Hotline (1-800-MH-Hyper or 1-800-644-9737)

Receiving Health Care Facility Existing transfer agreement Inpatient capabilities Adult/Pediatric Critical Care Continuous temperature and cardiopulmonary monitoring Non-invasive/invasive cooling Continuous sedation Dantrolene Dysrhythmia treatment Hemodialysis Transfer of Care poster Transfer agreements must be arranged in advance with a facility that meets state, federal and accreditation requirements

Receiving Health Care Facility Consultant Availabilities Anesthesiology Critical Care Hematology Surgery Nephrology Medical Toxicology Transfer of Care poster: Hematology: MH complicated by DIC in 13% of cases (MH clinical presentation paper) Surgery: Complete aborted surgery, treat compartment syndrome Nephrology: Renal dysfunction (due to ATN) complicated 7% of MH cases Toxicology: not MH but drug/recreational drug interactions

Report Data from ASC Cardiovascular signs Temperature and site Minute ventilation with ETCO2 Dantrolene amount given & response Muscular rigidity status Electrolytes I.V. site Urinary catheter & urine color Transfer of Care paper

Communication Coordination Direct communication concerning patient status & admission location between Anesthesia care provider at ASC AND Physicians accepting care at Receiving Hospital Transfer of Care poster

Transfer Decisions by On-Site ASC Health Care Professional Timing of Transfer Choice of Transfer Team Choice of Receiving Hospital Factor In: Transport time Bed availability Clinical stability Transfer of Care Poster May require ASC personnel and equipment to safely transfer MH patient (Personal Opinion: In most cases, health care professional should be the person with the greatest amount of anesthesia expertise)

Implementation of Transfer Decision Don’t delay transfer pending specific personnel or equipment availability if emergent transfer is mandatory **Accompany patient with appropriate medications and equipment if needed to serve the best interests of the patient **Personal Recommendation Transfer of Care protocol May require ASC personnel and equipment to safely transfer MH patient **(Personal recommendation: In most cases, the health care professional should be the person with the greatest amount of anesthesia expertise. Work out command issues within the transport vehicle prior to an MH event.) *Not a quote from the transfer guidelines)

Photographic credit to the Post and Courier (Charleston, SC)

Photographic credit to the Post and Courier (Charleston, SC)

Create Your Own ASC MH Transfer Plan Start with Guidelines Research available transport teams Consult with physicians at referral hospitals Research your interaction with the transport team if you want to treat your patient in the transport vehicle.

Clinical Characteristics 24.1% Emergency Sux 3.8 times more often Orthopedic, ENT, General Surgery Sux 1.9 times more often Temperature Monitoring (n=259) 14% skin liquid crystal sole probe In 10 patients, skin liquid crystal didn’t trend with core temp probe MH Clinical Presentation Paper 99.3% pulse ox 96.2% capnography 90.9% temp monitoring For skin liquid crystal temperature probe non-trenders: Tmax was 40.0 deg C 26 with no temp probes: no sign’t difference in induction-1st adverse sign. However, for 5/26 patients there was a rapidly inreasing temperature or increased temperature with median max temp of 39.1 deg C

Anesthetic Triggers (n=284) MH Clinical Presentation Paper Type of anesthetic agent administered prior to 284 malignant hyperthermia events. In two patients with missing data, we know that a volatile anesthetic was discontinued but whether succinylcholine was also used was not documented. 0.7%=2 cases 0.4%=1 case The no sux, no volatile patient was 2 years old with a suspected family history of malignant hyperthermia susceptibility undergoing a dental procedure. All but one administration of succinylcholine was intravenous. Volatile anesthetics included: halothane (15.6%), enflurane (2.8%), isoflurane (57.8%), desflurane (12.1%), and sevoflurane (20.6%).

Presentation 99% Respiratory Acidosis 26% Metabolic Acidosis 80% Muscular Abnormalities MH Clinical Presentation Paper All but one of the metabolic acidosis cases had respiratory acidosis as well. The majority did not have metabolic acidosis.

Clinical Presentation Pattern (n=196) % +Respiratory +Metabolic +Muscular 20.4 +Respiratory +Metabolic –Muscular 5.1 +Respiratory –Metabolic +Muscular 58.2 –Respiratory +Metabolic +Muscular 0.5 +Respiratory –Metabolic –Muscular 15.3 –Respiratory –Metabolic +Muscular MH Clinical Presentation Paper This Table lists the distribution of the 196 malignant hyperthermia events with data permitting evaluation for the presence () or absence () of respiratory acidosis, metabolic acidosis, and/or muscular presentations. Presentation type not associated with varying combinations of volatile anesthetics and succinylcholine.

Dantrolene Dosage (n=229) Dose Median 1st Q 3rd Q Range Initial (mg/kg) 2.4 1.9 2.8 .01-15.0 Initial (vials) 8 3 11 1 - 58 Total (mg/kg) 5.9 3.0 10.0 .02-100.0 Total (vials) 17 7 36 1 - 343 MH Clinical Presentation Paper This Table contains data on dantrolene doses used during 229 malignant hyperthermia events. Initial doses are reported for 228 events because there was 1 unreported initial dose. Initial number of vials=unreported data in paper Total dose: in 25% of patients more than 36 dantrolene vials were required Dantrolene is supplied in 20 mg/vial of lyophilized crystals that are mixed with sterile water prior to use.

Adjunctive Treatment (n=284) % Hyperventilation with FiO2=1 87 IV fluid loading 77 Active cooling 70 Bicarbonate 54 Anesthesia circuit change 48 Mannitol 34 Furosemide 32 Glucose and insulin 14 MH Clinical Presentation Paper Time from 1st sign to volatile anesthetic discontinuation was 10 minutes with 1st quartile 2, 3rd quartile 30 minutes. Less frequent but more than 1 subject and in order of decreasing frequency: CPR, calcium, lidocaine, procainamide, epinephrine, vasopressors, dopamine, defibrillation, norepinephrine, atropine, bretylium, hemodialysis, phenylephrine (see Table 5). Treatment frequency correlated with the severity of abnormal findings. (See Appendix B).