RT Book, Section
A1 Tinklepaugh, Mark S.
A2 Atchabahian, Arthur
A2 Gupta, Ruchir
SR Print(0)
ID 57260727
T1 Chapter 33. Porphyria
T2 The Anesthesia Guide
YR 2013
FD 2013
PB The McGraw-Hill Companies
PP New York, NY
SN 978-0-07-176049-2
LK accessanesthesiology.mhmedical.com/content.aspx?aid=57260727
RD 2024/04/25
AB Pathophysiology:Autosomal  dominant  defect  in  heme  synthesis;  90%  of  gene  carriers  are  asymptomatic;  80%  of  symptomatic  patients  are  women  from  puberty  to  menopauseHeme  is  a  porphyrin  critical  in  the  formation  of  hemoglobin  and  cytochrome  P450  complex  (drug  metabolism)Aminolevulinic  acid  (ALA)  synthase  is  the  enzyme  involved  in  the  rate-limiting  step  of  heme  formation:  Glycine  +  succinyl  CoA  →  ALAALA  synthase  is  induced  by  feedback  inhibition  when  heme  requirements  increasePartial  enzyme  defect  in  heme  pathway  leads  to  buildup  of  ALA  and  other  intermediaries  leading  to  neurotoxicity,  especially  when  need  for  heme  (catabolism  increased  by  menstrual  hormones)  or  need  for  cytochrome  P450  enzymes  by  inducing  drugsClassified  as:Erythropoietic  porphyrias:Günther  disease  and  protoporphyriaPatients  are  children;  no  acute  crisesHepatic  porphyrias:Cutaneous  porphyriaAcute  porphyrias  with  related  symptomatology  (most  often  problematic  with  anesthesia):  Acute  intermittent  porphyria  (AIP),  most  common  formVariegate  porphyria  (VP),  protoporphyrinogen  oxidase  deficiencyHereditary  coproporphyria  (HC),  coproporphyrinogen  oxidase  deficiencyPlumboporphyria  (PP),  ALA  dehydrase  deficiencyPrecipitating  factors:Clinical  conditions:Dehydration,  fasting,  infection,  emotional  stress,  hormonal  changes  (menstruation/pregnancy),  alcoholEnzyme-inducing  drugs:Barbiturates,  etomidate  (Amidate®),  ethanol,  hydantoin  anticonvulsants,  phenytoin  (Dilantin®),  hormonal  steroids  (progesterone,  estrogen)Lab  diagnosis:Urgently:  urinary  porphyrin  precursors  (delta-ALA  and  porphobilinogen)Porphyrins  in  urine  and  stool  (uroporphyrin,  coproporphyrin,  protoporphyrin)Specialized  lab:  enzyme  activities,  gene  mutationChem  7:  Hyponatremia  due  to  SIADH,  more  common  if  neuro  involvementTreatment  of  crisis:Analgesia  (morphine),  anxiolysis  (benzodiazepine,  phenothiazine)D10%  at  125  mL/hHeme  arginate  3–4  mg/kg  per  day  IVSS  over  30–40  minutes  ×  4  days;  very  effective  on  digestive  symptoms;  will  prevent  neurological  symptoms,  but  not  effective  if  already  present.  Possible  thrombophlebitisOther  symptomatic  treatment  as  needed  (e.g.,  beta-blockers  for  tachycardia)