Hipertermia

Maligna
Dra. Ana Julia Maycomea
Sombra

INTRODUCCI
N
Hiperter
mia
Maligna

Trastorno
hereditari
o

Succinilcol
ina
Halogenad
os
Agentes
desencadena
ntes

Sndrome
hipermetablico
Rigidez
muscular
Hipercapnia
Acidosis
Arritimias
Hipertermia

Chestnut: Obstetric Anesthesia: Principles and Practice, 3rd ed. Copyright 2004 Mosby, Inc.

INCIDENCIA
La incidencia clnica de HM
en la poblacin depende de
la susceptibilidad a la HM
y el uso de anestsicos
La incidencia de episodios de
HM en la poblacin general es
de
1:100 000
anestesias
Es ms frecuente en (2:1) y
< 19 aos (45-65%)

Malignant hyperthermia: Clinical diagnosis and management of acute crisis. Ronald S Litman, DO, FAAP. 2015 UpToDate

INCIDENCIA
Sndrome fulminante (rigidez
muscular, acidosis,
hipercalemia, arritmias,
hipertermia, aumento CK,
mioglobinuria):
1 /220 000 pacientes AGB
1/62 000 -Succinilcolina+
halogenado

Pocos reportes en embarazadas y

parturientas
Anestesia regional
Frecuencia baja
Chestnut: Obstetric Anesthesia: Principles and Practice, 3rd ed. Copyright 2004 Mosby, Inc.

Los pacientes susceptibles tienen

Durante un episodio de MH, las
anormalidades genticas en los
manifestaciones clnicas son debidas al
receptores de m. esqueltico,
hipermetabolismo celular: contraccin
permitiendo una acumulacin excesiva
muscular,++rabdomiolisis, metabolismo
de Ca en presencia de ciertos
anaerbico, acidosis, etc.
anestsicos.

Trastorno en la
regulacin del
calcio en el m.
esqueltico

FISIOPATOLOGI
A
Receptor de
RYR
(canal calcio del
RS)

Susceptible HM

Onda de despolarizacin

Umbral de activacin
RYR

Agentes desencadenantes
Liberacin de
Ca al citosol
Liberacin Ca++
Contraccin
Interaccin demiosina y actina
Uso energa (ATP)
, consumo O2, CO2 ,
Contraccin Muscular
lactato, calor

Contractura irreversible

CK, K+, mioglobina, H. sensible a lipasa,

Ca+ intracelular

Hipertermia maligna
En personas predispuestas geneticamente expuestas a:
Anestesicos (halotano), cafena,
neurolpticos (fluofenacina), ejercicio

Desacople de fosforilacin oxidativa

Aumento de calcio
intracelular

Falla de mecanismos
reguladores de liberacin de
calcio

Contractura

calor
hipermetabolismo

rabdiomilisis
O2
mioglobina

Falla renal

CO2

H+

K+

Arritmia cardiaca

efectores

Taquicardia

Dao cerebral

GENTICA
MH es un trastorno
heterogneo con defecto de
ms de un gen responsable
de la produccin del
sndrome clnico
Autosmico
dominante con
penetrancia variable

Chestnut: Obstetric Anesthesia: Principles and Practice, 3rd ed. Copyright 2004 Mosby, Inc.

AGENTES
DESECADENANTES
Anestsicos voltiles
Halotano
Isoflurano
Sevoflorano
Desflurano
Enflurano

Relajantes musculares
Succinilcolina
Chestnut: Obstetric Anesthesia: Principles and Practice, 3rd ed. Copyright 2004 Mosby, Inc.

EMBARAZO E HIPERTERMIA MALIGNA:

FISIOLOGIA MATERNA
EMBARAZO NORMAL
Metabolismo basal, consumo O2,
vent/min,

HCO3, buffer base

(mantener pH normal),

Alcalosis respiratoria compensada

(* HM )

Compresin AortoAcelera la acidosis

Cava

durante una
crisis

GC, TA,
perfusin
uterode
HM
plancenta

Analgesia
Obsttrica
PARTO
Metabolismo basal, consumo O2,,
vent/min

Piruvato y lactato (metabolismo

anaerobio y aerobio)
+
Hiperventilacin durante contraccin
Hipoventilacin entre contracciones
PaO2

EFECTOS EN EL FETO Y EL RECIEN

NACIDO

HM es una enfermedad
autosmica dominante
= 50% si el padre es
susceptible

Evitar los agentes

desencadenantes

MANEJO DE LA PACIENTE SUSCEPTIBLE DE HM

ANALGESIA
Canalizar
Monitorizar temperatura, FC, TA, ECG
Evitar compresin aorto-cava

COMMON ANESTHETIC DRUGS AND

THEIR SAFETY IN MH-SUSCEPTIBLE
WOMEN
Drug
Route
General
Anesthetic
Agents
Induction
AgentsAgents
Local Anesthetic
Halothane, enflurane, Inhalation
Sodium
thiopental
Intravenous
Bupivacaine
Regional
isoflurane,
Propofol
Intravenous
sevoflurane,
Lidocaine
Regional
desflurane
Etomidate
Intravenous

Intravenous
Nitrous oxide
Inhalation
Ketamine
Intravenous
Ropivacaine
Regional
Benzodiazepines
Intravenous
2-Chloroprocaine
Regional

Use

Safe MH

Anesthesia, uterine
Induction
Analgesia/anesthesia
relaxation
Induction
Analgesia/anesthesia
Induction
Intubation/arrhythmia
Analgesia/anesthesia
Analgesia/induction
Analgesia/anesthesia
Amnesia/anxiolysis
Analgesia/anesthesia

No
Yes
Yes

Muscle
relaxation
Analgesia
Muscle
relaxation
Analgesia

No
Yes
Yes

Intravenous
relaxation
Regional, intravenous Muscle
Analgesia

Yes

Neuromuscular
Blocking Agents
Opioids
Succinylcholine
Intravenous
Fentanyl
Regional, intravenous
Rocuronium
Intravenous
Meperidine
Regional, intravenous
Atracurium
Morphine

Yes
Yes[*]
Yes
Yes
Yes

PRESENTACIN
CLNICA

Tachycardia
Tachypnea
Masseter spasm

Generalized
rigidity
Elevated endtidal
concentration

Cyanosis

Arrhythmia
Acidosis
Hyperkalemia
Hyperpyrexia
Myoglobinuria
Increased CK level

Malignant hyperthermia: Clinical diagnosis and management of acute crisis. Ronald S Litman, DO, FAAP. 2015 UpToDate

CARACTERSTICAS CLNICAS

Signos
tempranos

Hipercapn
ia
Rigidez
del M.
Masetero
Rigidez
Muscular
Generaliza
da

Signo ms temprano
Hipercapnia resistente al
aumento de ventilacin minuto
AGB + Ventilacin
espontnea= etCO2 >60
mmHg y PaCO
mmHg
Incapacidad
para
abrir
la boca
2 >65
de un paciente despus de la
administracin de un agente
desencadenante
En presencia de bloqueo
neuromuscular se considera
patognomnico de MH

Malignant hyperthermia: Clinical diagnosis and management of acute crisis. Ronald S Litman, DO, FAAP. 2015 UpToDate

CARACTERSTICAS CLNICAS

Signos Tardios

Cambios EKG
relacionados a
K+
Ventricularectop
y/ bigeminy
Taquicardia/
Fibrilacin
ventricular
Hipertermia

Mioglobinuria

Generalmente es un signo
tardo
Usualmente ausente en el dx
inicial
Coluria (coca cola)
Inicia a las 14 hrs despues del
inicio de la crisis

Sangrado
Excesivo
Malignant hyperthermia: Clinical diagnosis and management of acute crisis. Ronald S Litman, DO, FAAP. 2015 UpToDate

PREVALENCE OF CLINICAL SIGNS DURING MH

EPISODE
Clinical sign

Percentage with
sign

Hypercarbia

92.2

Sinus tachycardia

72.9

Rapidly increasing
temperature

64.7

Elevated temperature

52.2

Generalized muscular
rigidity

40.8

Tachypnea

27.1

Masseter spasm

26.7

Sweating

17.6

Cola-colored urine

13.7

Cyanosis

9.4

Ventricular tachycardia

3.5

Data from: Larach MG, Gronert GA,

Allen GC, et al. Clinical presentation,
treatment, and complications of
malignant hyperthermia in North
America from 1987 to 2006. Anesth

LABORATORIO
Mixed metabolic
and respiratory
acidosis
Hiperkalemia
Creatine
Kinase and
Myoglubinuria
Chestnut: Obstetric Anesthesia: Principles and Practice, 3rd ed. Copyright 2004 Mosby, Inc.

LABORATORY VALUES IN ACUTE

MALIGNANT HYPERTHERMIA
Laboratory study

Typical value in MH

Patient conditions

>20,000 international units

With succinylcholine

>10,000 international units

Without succinylcholine

Urine myoglobin

>60 mcg/L

Serum myoglobin

>170 mcg/L

Serum K

>6 mEq/L

Without renal failure

>60 mmHg

During controlled ventilation

>65 mmHg

During spontaneous
ventilation

Arterial pH

<7.25

Base excess

Below 8 mEq/L

Creatine kinase

PaCO2

Typical laboratory values used to confirm the diagnosis of acute malignant hyperthermia.
Source: Larach MG, Localio AR, Allen GC, et al. A clinical grading scale to predict malignant hyperthermia susceptibility.
Anesthesiology 1994; 80:771.

DIAGNSTICO
CLNICO
Durante el evento agudo, el diagnstico
es presuntivo, en base a la presencia de
1 o ms de las manifestaciones clnicas
tpicas asociadas a HM.
El dx debe ser considerado en todos los
px que reciben agentes desencadenantes
Cerca del 90% de los px tienen APP y
AFP negados

An increased ETCO2level (>55 mmHg),

which does not normalize with increasing
ventilation
Generalized muscle rigidity, especially
in the presence of neuromuscular blockade
Hyperkalemia-related arrhythmias and
electrocardiographic changes
Tachycardia (not explained by clinical
scenario)
Tachypnea (not explained by clinical
scenario)
Myoglobinuria
Hyperthermia

CLINICAL INDICATORS OF ACUTE MALIGNANT HYPERTHERMIA

Fever
Rigidity
Tachycar
Acidosis
dia

Rhabdomyol
ysis
Other

Generalized ventilation:
muscular
rigidityin(sustained
contracture)
during
Controlled
Inappropriate
rapid increase
temperature
(judgement)
anesthesia
with triggering agents
PETCO2>55
Inappropriate perioperative temperature >38.8C (judgement)
Severe
masseter
muscle spasm shortly following succinylcholine
PaCO
>60
2
administration
Inappropriate
tachycardia
Spontaneous sinus
ventilation:
CK >20,000 international units after anesthesia with
PETCO2>60
succinylcholine
Ventricular tachycardia or ventricular fibrillation
PaCO2>65
CK >10,000
international units after anesthesia without
succinylcholine
BaseInappropriate
excess belowhypercarbia
8 mEq/L (judgement)
Cola-colored urine in perioperative period
Arterial
pH <7.25 tachypnea (judgement)
Inappropriate
Urine myoglobin >60 mcg/L
Rapid reversal of MH signs with dantrolene
Serum myoglobin >170 mcg/L
Serum K >6 meq/L (without renal failure)

DIAGNSTICO
Type
Moderate
Fulminant/classic

Mild

Symptoms/signs
Risk
Inconclusive
signs of MH involving metabolic and
0.88
Metabolic acidosis
0.96
muscle abnormalities, with MH the probable diagnosis
Muscle rigidity

Signs of metabolic derangement (pH > 7.3, body core

0.14
Hyperthermia
(>38.5

temperature 38.5
C)C)
CK
level > 1500, myoglobinuria
Arrhythmias
0.76

Masseter
spasm with

rhabdomyolysis

Hyperkalemia
Masseter spasm with signs of Arrhythmias, rising core temperature
metabolic disturbance
Myoglobinuria

Masseter
spasm only
Increased CK level
Unexplained perioperative

death or cardiac arrest

Other
Postoperative pyrexia or rhabdomyolysis

0.57

0.28
0.66
0.07

LABORATORIO
Arterial blood gas with pH <7.25, base excess
below -8mEq/L
K >6mEq/L

No se requiere para el
diagnstico
presuntivo
Creatine kinase (CK)

>10,000 international units (without

succinylcholine)

>20,000 international units (withsuccinylcholine)

Serum myoglobin >170mcg/L

Urine myoglobin >60mcg/L

LABORATORIO
Prueba de contractura
Cafena/Halotano positivo.
Es el estndar de oro para el diagnstico de
Hipertermia
Maligna
Espectroscopia
de RMN como prueba
Durante la prueba, se expone el tejido fresco a halotano y
de cribado no invasivo para MH.
cafena y se mide el grado de contraccin.
Sensibilidad de 97% y especificidad 78%

DIAGNSTICO DIFERENCIAL

Anestesia/ciruga
Insuficiente
anestesia/anestesia
Insuficiente ventilacin/flujo
de gas fresco
Mal funcionamiento maquina
Sobrecalentamiento
Absorcin incrementa de CO2
durante laparoscopia

Present
Presentes
Taquicardi
es

Hipercapnia
a
Ac.Hipertensi
Respiratoria
Presentes
Taquicardia
n
Insuficiencia
Hipertensin
Taquipnea
ventilatoria
CO2
Hipercapnia

Ausentes
Ausentes
Signos

Acidosis
musculares
metablica
Ausentes
Hipercapnia
Signos
Hipertermia
musculares

DIAGNSTICO
DIFERENCIAL
Presentes

Relacionados a Frmacos
Anafilaxia
Reaccin a transfusin
Abuso de drogas
Abstinencia a alcohol
Sx Neuroleptico maligno
Sndrome Serotoninrgico
Efectos extrapiramidales de farmacos
antisicoticos
Contaminantes pirogenos

Broncoespasmo
Sibilancias
presin va
Presentes
area
Fiebre
obscura
vent/min
Orina
PaCO2
Hipotensin
Cocana:
S. y s.
Hipercalemia
MDMA:
dermatolgicos
Metanfetaminas

Ausentes
Signos
Ausentes
musculares
Signos
musculares

DIAGNSTICO DIFERENCIAL

Relacionados a
Frmacos
Infeccin/Septicemia
Feocromocitoma
Tormenta tiroidea
Patologa cerebral
Desordenes neuromusculares
Rabdomiolisis

Presentes

Fiebre
Acidosis
metbolica
Presentes
CK
Hipertensin
Taquicardia,
severa
arritmia,
Taquicardia
hipertermia
Hipotensin y
colapso CV

Ausentes

Rigidez
generalizada

Ausentes
Signos
musculares

DIAGNSTICO DIFERENCIAL DE HIPERTERMIA Y

TAQUICARDIA EN EL EMBARAZO

DIFFERENTIAL
DIAGNOSIS
OF FEVEROF
DIFFERENTIAL
DIAGNOSIS
Hipertermi
DURING
PARTURITION
Taquicardia
TACHYCARDIA DURING PARTURITION

Infection: chorioamnionitis, urinary tract infection, other infections (e.g.,

influenza, viral illness)

Fever
Respuestas

Anxiety
normales:
Environmental temperature

Blood loss dolor,

ansiedad y
Epidural anesthesia
Hypotension fiebre
Deshidratacin e
Dehydration/labor
infeccin
Drug reactions: cocaine, atropine,
beta MH
(corioamnioitis, IVU)
adrenergic tocolytic agents
Drug reactions: cocaine, atropine, tricyclic antidepressants,

MH oxidase (MAO) inhibitors, neuroleptic malignant syndrome,

monoamine
prostaglandins

MANAGEMENT OF MH CRISIS
6.
hyperkalemia
withagents.
glucose
1. Treat
Discontinue
all triggering
and
insulin.

2. Hyperventilate
with 100% oxygen.
7.
Treat
arrhythmias
with
procainamide.
Disconnect vaporizers if possible. Change carbon dioxide absorbent and tubing
(Arrhythmias
may
not
develop
if dantrolene
is
when
possible. (The machine
does
not have
to be changed
immediately.)
3. Administerearly.)
dantrolene
2.5 mg/kg intravenously
administered

(up
10 mg/kg).

8.to
Cool
the patient
(e.g., cold intravenous
4. Continue
dantrolene
untillavage
temperature,
heart
solutions,
cooling
blanket,
of body
rate, andwith
end-tidal
cavities
coldCO
solutions).
2 return tonormal.
9.
Maintain
urine
output
with fluids, mannitol,
5. Perform
serial
blood
gas measurements.
Treat
and/or

acidosisfurosemide.
with sodium bicarbonate
1 to 2 mEq/kg.
10. Postoperatively, counsel the patient and
refer her for muscle biopsy.

ACUTE TREATMENT

Call for help:Call for MH equipment and drug cart; notify the surgeon;
complete surgical procedure as soon as feasible; callMH Hotline: 1-800-6449737(US); outside US: 1-209-417-3722

Initiate support:Discontinue inhalational agents and succinylcholine;

hyperventilate with 100% oxygen; use non-triggering agents for the
remainder of the procedure; intubate with endotracheal tube
Give dantrolene:Initial bolus dose 2.5 mg/kgIV rapid continuous push.
Continue to administer dantrolene in 1 mg/kg increments until symptoms
abate (ie, hypercarbia and/or rigidity resolve).
Dantrium and Revonto vs Ryanodex

Watch for reversal of clinical signs (end tidal CO 2should begin to normalize);
repeat as needed. Cumulative total doses up to or exceeding 10 mg/kg may
occasionally be required

ACUTE TREATMENT

Get blood gas/labs:Venous gas (femoral) may be better than arterial gas to
follow hypermetabolism
Give bicarbonate for acidosis:Sodium bicarbonate 1 to 2 mEq/kg IV push
over 5 to 10 minutes
Cool the patient:Start when core temp >39C; stop when core temp <38C;
cold saline for infusion; ice to body surface; lavage body cavities (eg,
stomach, bladder, rectum)

ACUTE TREATMENT

Treat hyperkalemia:Hyperventilate, stabilize cardiac membranes with calcium

Calcium chloride:Adults: 0.5 to 1 gram (5 to 10 mL of 10% solution) per dose; pediatric:

10 to 20 mg/kg (0.1 to 0.2 mL/kg 10% solution), maximum of 2 grams (20 mL) per dose;
repeat after five minutes if ECG changes persist; or
Calcium gluconate:Adult: 1.5 to 3 g IV (15 to 30 mL of 10% solution) per dose;
pediatric: 60 to 100 mg/kg (0.6 to 1 mL/kg 10% solution), maximum of 3 grams (30 mL) per
dose
Sodium bicarbonate:1 to 2 mEq/kg IV push over 5 to 10 minutes (maximum 100 mEq
per dose); do not give sodium bicarbonate in the same line as calcium
Insulin and dextrose:Adult: 10 units regular insulin IV push with 50 mL of 50%
dextrose; pediatric: 0.1 units insulin/kg IV push with 0.5 grams/kg dextrose (eg, 1 mL/kg 50%
dextrose or 2 mL/kg 25% dextrose); monitor fingerstick glucose closely
Treat dysrhythmias:Dysrhythmias usually respond to treatment of acidosis and
hyperkalemia; use standard ACLS protocols

ONGOING CARE

Continue dantrolene:Once acute MH is under control, administer 1 mg/kg

every four to six hoursor0.25 mg/kg/hour as a continuous infusion. Maintain
dantrolene infusion or interval dosing for at least 24 hours; further dosing
may be indicated. Protect dantrolene from light; once reconstituted,
dantrolene is stable for six hours.

SEGUIMIENTO

Urine output: Maintain at 1 to 2 cc/kg/hour; insert Foley catheter if patient's

consciousness is depressed
Temperature: Maintain <39C aggressively;be wary of hypothermia if
temperature decreases below 38C
Blood gas: Normalize pH; optimize pCO 2and pO2

Electrolytes: Normalize
Glucose: Check hourl
Creatine kinase: Check CK every 8 to 12 hours; alkalinize urine and increase
flow >1 to 2 mL/kg/hour if CK >10,000 international units/Ly and correct

Coagulation parameters: Watch for disseminated intravascular coagulation

(DIC), especially if hyperthermia is >42C