Case of xenobiotic induced cyanosis

Dr.s.a.jayakumar IMCU chief -Prof. Dr.Chenthil

CASE 1Mr.Suresh 35/male

Admitted on 24.12.2010

Alleged h/o ingestion of some oil ?carburetor oil

He was found lying unconscious with a can of oil beside him; He had vomitted and he was covered with

vomitus ;

Past history : not a DM/HT/IHD/ BA/TB patient

Personal history : chronic alcoholic > 15 yrs -360 ml /day

Unconscious GCS E1 V1 M1Tachypneic Dyspnoeic Cyanosis + fingers toes , lips & tongue

Pulse : 110/mt BP : 80/60 mmhg RR: 30/mt

SpO2 :85 % ABG

p H 7.36 p O2- 107 p CO2 -32.6

Immediately patient was intubated & put on ventilator ;on ACMV mode;with FiO2 100%;

IVFDopamine infusion started at 10µg/kg/mt

Inj .methylene blue 1 mg/kg infusion given

Hb – 12.0 g/dl;TC- 9600; P80 ;L20;ESR - 5/12 mm;PCV-36%;Platelets -1.8 lakhs

RBS – 122 mg/dl;Urea- 26 mg/dl;Creatinine – 0.8 mg/dl

Na-138meq; k-4.8 meqCl -96meq;Hco3-22meq

Serum meth Hb -- ++

course after treatment;

initially patient improved consciuosness after 2 doses of methylene blue ;Cyanosis improved;Obeying commands ;

Within 2 days ,he developed fever ,progressive dyspnea ,extensive crepitations and despite antibiotics ,ventilatory support & other supportive measures died on the third day of admission ;

Case 2 Mrs.Devi , 28 yrs female

Admitted on 13.03.2011 ;

Alleged to have consumed some amount of a

product ‘ hytro-zyme ‘

Nitrobenzene

She was found unconscious in her house ,

with deep irregular breathing and secretions from mouth ;

Past history : not a DM/HT/IHD/BA/ patient

Personal history : regular menstrual cycles ; takes mixed diet

Unconscious E4 V1 M4DyspneicTachypneicCyanosis of lips,tongue ,fingers &

toes

Pulse 100/mt;BP- 90/60 mmhg ;RR- 34/mt

SpO2 -80%

ABG p H 7.4 p O2 128 p CO2 34

Immediately patient was intubated & connected to ventilator –ACMV mode with FiO2 -100 %;

IVF

Inj.methylene blue 1mg/kg ;

Hb-10.2g/dl;TC- 9800; P86 L14;ESR-10/22PCV-30%;Platelet :1.5 lakhs;

RBS- 131mg/dl;Urea -31Creatinine -1.1

Na 134; K 4.5Cl -98; Hco3-22

Serum meth hb +

Course after treatment

Patients SpO2 was constantly around 80 % despite ventilatory support ;Consciousness didn’t recover ;

She developed progressive hypotension and stayed unconscious ;

After 2 days despite all available measures she died

Case 1 ingestion of ? carburetor oil –

organic solvent cyanosis hypotension Meth

hemoglobinemia Initial improvement

with methylene blue

Case 2 Ingestion of nitro

benzene

cyanosis, Hypotension Meth

hemoglobinemia No improvement

despite treatment ;

cyanosis

high flow O 2 ( improves)

(no improvement )

met hb conc.

< 25% >25%

asymptom. Symptom methyleneblue

no respon.

respon

Basics Reversible binding of oxygen to

hemoglobin is ‘oxygenation’;Whereas oxidised hemoglobin is a

state where ferrous iron is converted to ferric

iron; such a hemoglobin (oxidised

hemoglobin)is called “meth hemoglobin “

Normally met Hb level is in the body < 1 % ;

Protective mechanisms

When there is a basic defect in the protective mechanisms

( HEREDITARY ) or When there is an external agent which

overwhelms the protective

mechanisms ( ACQUIRED )

clinically significant methhemoglobinemia results

HEREDITARY METHHEMOGLOBINEMIA

Deficiency of diaphorase I(NADH met Hb reductase):

type 1 - 85% ; autosomal recessive ; only mature red cells are affected;

type 2 - 10 -15 % of cases ; all cells are affected ;

developmental delay & early death ;

Hemoglobin M disease : autosomal dominant ; either alpha or beta

globin affected

other causes: pyruvate kinase deficiency G6PD deficiency

METH HAEMOGLOBINEMIA

Acetanilidp-Amino salicylic acidAniline dyes

Benzene derivativesClofazimine Chlorates

ChloroquineDapsoneBenzocaineLidocainePrilocaineMenadione

MetoclopramideMethylene blue*

Naphthoquinone

NaphthaleneNitritesAmyl nitriteFarryl nitriteSodium nitrite

NitroglycerinNitric oxideNitrobenzeneParaquatPhenacetinPhenazopyridine

PrimaquineResorcinol

Sulfonamides

Pathogenesis

Met Hb causes - decreased available O2 carrying

capacity ; -increased affinity of unaltered Hb FOR o2

,shifting the oxygen dissociating curve to left ;

Cyanosis develops when 1.5 g/dl met hb is present ;

Also depends on the rate of formation and elimination

of MetHb

1 - < 3 % Asymptomatic

3 – 15 % Slate grey color

Low SpO2

15 – 20 % Cyanosis Chocolate brown blood

20 – 50 % Dyspnea , dizziness,exercise intolerance ,syncope ,headache weakness

50 – 70 % Tachypnea ,arrhythmia ,metabolic acidosis ,seizures ,CNS depression ,Coma

> 70% Grave hypoxia ,death

Investigations PULSE OXIMETER :

-non invasive method; measures SpO2 ;

-2 light emitting diodes –measure absorbance at peak

wavelength for oxy & deoxy Hb – 940 & 660 nm respectively ;

-presence of meth Hb ,sulf Hb interfere with the accuracy of pulse oximeter;

presence of methylene blue too interferes

LP 15 defibrillator /pulse

oximeter ;

Advantage of monitoring meth hemoglobin

ABG

In cases of meth hemoglobinemia when there is cyanosis

and the SpO2 is abnormal with the help of ABG we can find out

that the PO 2 normal ; as the ABG is not affected by the abnormal hemoglobin

Co oximeters :

it is a spectrometer ;

uses 4 wavelengths of light;

measures oxyHb, deoxyHb, carboxyHb

& metHb

Met hb assay Quantitative test is by EVELYN MALLOY

method Take 2 aliquots of blood 1 & 2 ; 1) Absorbance measured at 630nm

(A1);add pot.cyanide; measure again absorbance(A2) ; if any met hb + the cyanide will abolish the absorbance peak

2)add pot.ferricyanide;all Hb converted to metHb;now measure absorbance before(A3) and after adding cyanide(A4) ;

% of met Hb = ( A1-A2)×100 / (A3-A4)

Treatment: 1.methylene blue; 1-2mg/kg infused over 5

mts ;not exceed 7mg/kg; clinical improvement seen within 1 hr ; contraindicated in G6PD deficiency 2. Hyperbaric oxygen ;3.Exchange transfusion ;NOTE: Blood transfusions and ascorbic acid are of

unproven value ;

CERTAIN INTERESTING ANECDOTES : 1. Ernst Felix Immanuel Hoppe-Seyler

german scientist first described meth hemoglobin ;

2. hyperlipidemia may spuriously cause elevated methb levels ;

3. foods having high nitrate content which might cause methb

cauliflower carrot spinach & broccoli;

4.Well water with high nitrate content can cause meth Hb ;

5.Dapsone induced meth hemoglobinemia ; -- use cimetidine as it prevents the

formation of toxic metabolite of dapsone