Statistical modeling in pharmaceutical research and development.
Eclampsia
1. MANAGEMENT
OF
ECLAMPSIA
Dr Susanta Kumar Behera
Chairperson
DR RITANJALI BEHERA
1
2. Eclampsia is pre eclampsia with
convulsion and or coma
Or
Development of Convulsions and/or unexplained
coma during pregnancy or postpartum in
patients with signs and symptoms of
preeclampsia
What is the most common
causePRE EXISTING EPILEPSY
of seizure during
Pregnancy ?
2
3. Incidence :
o 1:500 to 1: 30 & Common in Primigravida (75%)
than multigravida (25%)
o In 80% cases it is proceeded by severe
preeclampsia
o Commonly occurs between 36th week to term
Types
a) Antepartum -50%
b) Intrapartum-30%
c) Postpartum-20%(Early & Late)
d) Intercurrent-Rare
3
6. CAUSES OF CONVULSION
Cerebral anoxia : spasm of cerebral vessel due to
hypertension-increase cerebrovascular resistance-
decrease oxygen consumption-convulsion
Cerebral edema –irritation
Cerebral dysarhythmia : increases following edema
& anoxia
Stages of convulsion
a) Premonitory : 30 Sec
• twitching of muscle
• rolling of eye ball & fixing.
6
7. b) Tonic (30 sec) : c) Clonic (1-4 min) :
• Tonic spasm of body • Alternate contraction &
relaxation of muscle
• Ceasing of respiration
• Congested face & Cyanosed
• Protruding of tongue • Conjunctival Congestion
• Fixing of Eye ball • Twitching starting from face
& spreading tongue biting
• Cyanosis
• Stertourous breathing with
froths
• Involuntary passage of
stool & urine
d) Coma :
-Persits for variable period & at times patient confused
-Deep coma may occurs (cerebral hemorrhage).
-Labor usually starts shortly after the fit. 7
11. MANAGEMENT
General
1) Maintenance of airway
2) Oxygen administration
3) Fluid Management
4) Organization of investigation
Control of Convulsions
Control of BP
Obstetric Management
Complication Management
Postpartum Care
Prevention
11
12. THE OBSTETRIC ICU PATIENT
INTENSIVE CARE UNIT
DELIVERY ROOM HDCU
POST ANESTHESIA
OPERATING ROOM CARE UNIT
12
13. GENERAL
Transfer of patient to hospital
Place the patient in a railed cot in isolated room.
Detailed history taking
Vital stabilizing(Control of BP)
Continuous drainage facility
Monitoring vitals & Urine Output
Antibiotics & H2 blockers
13
14. Patent airway with tracheal and bronchial
suction.
Nasogastric tube may be inserted .
IV glucose 25% as a Liver support, increases
UO & improves hemoconcentration.
Nursing Care
a) Mouth gag in between teeth
b) Clearing of air passage
c) Raising foot end of bed
14
16. FLUID THERAPY
IATROGENIC FLUID OVERLOAD IS THE MAIN CAUSE OF
MATERNAL DEATH IN ECLAMPSIA
Depends upon a careful balance between restriction
with possible exacerbation of end organ
hypoperfusion and renal dysfunction and volume
overload with pulmonary edema
PRINCIPLES :
• Accurate Recording of Fluid Balance
a) Delivery & Postpartum Loss
b) Input/Output Deficit
16
17. • Maintenance Crystalloid infusion :
1) Crystalloids is the choice of fluid-RL
2) Total daily infusion=UO+1000 ml
3) Fluid load : 80ml/hr or UO in Preceding hr+30 ml
4) No excess use of Crystalloids/Dextrose
• Selective Colloid expansion
• No unnecessary fluid overload before
regional anesthesia
- Severe refractory HTN
- Pulmonary Edema
- Oliguria unresponsive to fluid therapy
17
18. • Diuretics: Only in presence of PE/CCF
• Pulse Oximetry
• Selective monitoring of CVP if blood loss is
excessive
• Intraarterial pressure monitoring indicated
- Unstable eclamptic women
- BP is very high
- Obese women when noninvasive measurement
are unreliable
- Hemorrhage > 1000ml
- Severe Cardiac Disease
18
19. POSTPARTUM
• Urine output recorded hrly & each four hr block summated
• Each FOUR hr block should be > 80 ml
• If two consecutive four hour block fails to achieve 80 ml
Total Input > 750 ml in Total Input < 750 ml in
excess of U/O in last 24 hr excess of U/O in last 24 hr
20 mg IV Frusemide 250 ml Colloid
Colloid if diuresis > 200 over 20 min
ml in next hr
U/O < 200 ml U/O >200 ml
20 mg IV Baseline Fluid
Frusemide + 250 ml
Gelofusine 19
20. ANTICONVULSANTS
Magnesium Sulphate(1924)
Continuous IV
1) Continuous IV Regimen Regimen
2) Pitchard Regimen
3) Sibai Regimen 4-6 gm loading dose
4) Zuspan Regimen of Mg So4 in 100 ml of
Diazepam fluid IV slowly over
Phenytoin 15-20 min
Lytic Cocktail Regimen
a) Chlorpromazine 1-2gm/hr in 100 ml of
b) Promethazine IV maintenance
c) Pethidine
infusion
20
21. PITCHARD REGIMEN
Route : IM
4gm of 25% MgSO4 IV slowly over 5-10 min
followed by 5 gm 50% MgSO4 IM into each
buttock.
5 gm 50% MgSO4 IM 4hrly to alternate buttock.
MOA
1) motor end plate sensitivity to Ach & reduces
neuromuscular irritability
2) Blocking neuronal uptake of Calcium
3) Inhibits platelet aggregation.
4) Increase PGI2 synthesis.
21
22. SIBAI REGIMEN(1990)
6 gm MgSo4 over 20 min followed by 2 gm MgSO4
IV infusion
ZUSPAN REGIMEN(1978)
4 gm MgSo4 over 5-10 min followed by 1gm/hr
MgSO4 IV infusion
DIAZEPAM
10-40 mg IV slowly followed by 40 mg in 500 ml of
5%D at the rate of 30 drops/min
22
23. MAGNESIUM SULFATE
• Lazard in 1924,intern in California started mgso4.
• Given IV 20-25% (most commonly) or IM (50%) or
SC(15%)
• 6 gram load followed by 2 grams per hour
• Total dose should not >24 gm/24hr
• Supra therapeutic levels lead to CNS depression,
cardiac arrhythmias,
• Monitoring :
»Patellar reflex.
»RR >16/min.
»U/O >100ml/4hrs.
»Serum Mg++ level.
23
24. MAGNESIUM TOXICITY
Clinical Manifestation Serum Level
Physiologic 1.3-2.1 mEq/L
Peripheral Vasodilatation/Flushing
3-5 mEq/L
/Sense of warmth/Vomiting
Therapeutic 4-7 mEq/L
Depression of deep reflex ml of
Antidote – 10 7-8 mEq/L
10% Calcium
Arrest of Deep Reflex 8-10 mEq/L
Gluconate slow IV 10-12 mEq/L
Respiratory Depression
Respiratory Arrest 12-15 mEq/L
Arrhythmia/Heart Block/Bradycardia 15-20 mEq/L
Cardiac Arrest 2424242424 24
25. LYTIC COCKTAIL REGIMEN
Menon in India has started this regimen-1961
25 mg Chlorpromazine & 100 mg Pethidine in 20 ml
of 5%D IV +
50 mg Chlorpromazine & 25 mg Promethazine IM
50 mg Chlorpromazine & 25 mg Promethazine IM
alternatively 4 hrly X 24 hr
IV drip 10%D with 100 mg Pethidine at rate of 20-30
drop/min X 24 hr following last fit.
25
26. PHENYTOIN
10 mg/kg slow IV followed by 5 mg/kg after 2
hr
200 mg given orally after 12 hrs X 48 hrs
following delivery
Side effects : hypotension/cardiac arrhythmia
/phlebitis
ECG monitoring required
MOD. STROGANOFF METHOD
MgSO4 6gm IV initially then 4 gm/4hours IM +
20mg Morphine IM.
26
27. STATUS ECLAMPTICUS
• Consult anaesthetist
• Nasophayngeal Suction
• Intubation , IPPV & Muscle relaxation
• Medications
a) Inj Thiopentone Sodium 0.5 mg in 20 ml of 5D
IV slowly
b) Inj Diazepam 10 mg Slowly IV followed by 10
mg in 5D as IV drip
• General Anesthesia(PPV + Muscle Relaxants)
• Evaluation of Intracranial Abnormalities 27
28. • Investigations : CT/EEG/Cerebral Doppler
Velocimetry/MRI/Cerebral Angiography
• Cerebral imaging indicated in
1) Patients with Focal Deficits/Prolonged Coma
2) Atypical presentations of Eclampsia
- Onset before 20 weeks
- > 48 hrs following delivery
- Refractory to Magnesium Sulphate therapy
28
29. ANTIHYPERTENSIVES
Indicated if BP > 160/110 mm of Hg in spite of
Anticonvulsants & Sedatives
Common drugs
1) IV Labetalol
2) Oral Nifedipine
3) IV Hydralazine
4) Diuretics in presence of Pulmonary
Edema/CCF
If C/I of MgSO4 : Phenytoin: 15 mg/kg at 40 mg/min
with monitoring of Cardiac function and BP x 5 min
Therapeutic Range : 10-20 μg/ml. 29
30. COMMON AGENTS
Agent MOA Side Effects
Fatigue, Bradycardia,
Labetalol α β-Blocker
Swelling of Feet, Depression
Headache, Hypotension,
Nifedipine CCB
Palpitation, Constipation
Flushing, Hypotension
M-Dopa Direct PAV
Headache, Dry Mouth
Hydralazi Flushing, Headache,
Direct PAV
ne Diarrhea, Constipation
Sod. Nitr. Direct PAV Metabolite (Cyanide) 30
31. Agent Dose Max Dose
Oral : 25 mg 8 hrly
Oral : 300 mg
Hydralazine IV : 5-10 mg & repeat
IV : 20 mg
after every 10-20 min
Oral : 100 mg 12 hrly
Oral : 2400 mg
Labetalol IV : 20 mg & repeat 40-
IV : 300 mg
80 mg every 10 min
Nifedipine Oral :10 mg 6-8 hrly 120 mg
Methyldopa Oral : 250 mg 8 hrly 2 gm
Sodium Nitr. IV : 5 mcg/kg/min 10 mcg/kg/min
31
32. Eclampsia
Anticonvulsants/Antihypertensives+/-Diuretics
Not in Labor Labor
Fits Fits not ARM LSCS
controlled controlled
Ventouse
Obstetric
Forcep
Indication
32
33. FITS NOT
CONTROLLED
6-8 hrs
Termination
ASSESS INDUCTION SCORE
Favourable Unfavourable
ARM
OXYTOCIN INDUCTION
MISOPROSTOL LSCS
33
35. INDICATION OF LSCS
Uncontrolled fits in Spite of therapy
Unconscious patient and poor
prospect of vaginal delivery
Obstetric indication
a) Preterm (< 34 Week)
b) IUGR
c) Non reassuring FHR
d) Oligohydramnios
e) Malpresentations
f) Suspected AP
35
36. CARE DURING DELIVERY
• Care full monitoring of maternal & fetal status
• Delivery : Well Planned, done on the best Day,
performed in the best Place, by best Route and
with best Support team
• H2 antagonists & Antibiotics
• Vaginal delivery Preferred if not indicated
otherwise
• Local infiltration of anesthesia for all VD
36
37. • No prophylactic MethylEgrometrine/Symtometrine
• Cut Short of Second stage of labour
• Prophylactic Rectal Misoprostol
• Managing 3rd Stage : 5-10 units of IV Syntocinon /
Inj Prostaglandin
• Vigilant about PPH & Prompt Management
• Prophylaxis against thromboembolism
37
38. POSTPARTUM CARE
• Continuing MgSo4 following 24 hr of
delivery/last Seizure.
• Regular Monitoring of BP 4 hrly
• MONITORING OF VITAL X 48 HRS
• Antihypertensive till BP < 150/100 mm of Hg
• Discharged on 4th Puerperal day
• Regular intake of Iron & Calcium
38
39. CHOICE OF ANESTHESIA
• Local Anesthesia
• Pudendal Block
• Regional Anesthesia : Spinal Or Epidural
a) Preferred for LSCS/Labor
b) Decreased Maternal Morbidity & Mortality
c) Epidural preferred over spinal due to provocation of
excessive hypotension
-Superior pain relief
39
40. -Epidural Promotes Utero-Placental Blood Flow
-Extended to Provide Regional Anesthesia for
ID/CS
• General Anesthesia
Indicated
a) Coagulopathy / Pulmonary Edema / Impaired
Consciousness
b) Failed Spinal /Epidural block
c) Inadequate time to perform/extend a block
Difficulty intubation due to laryngeal edema
Risk of ICH & Aspiration Pneumonia
40
42. FETAL MONITORING
• Done by
a) DFMC
b) USG-GA/AFI/FW
c) BPP/CTG
d) Color Doppler of MCA/Ut A/UA/DV
• Maternal hypoxemia & hypercarbia : FHR & Uterine
Changes
a) FETAL : Bradycardia/Transient Late deceleration/decreased
beat to beat variability & Compensatory tachycardia
42
43. b) MATERNAL : frequency & tone of Ut. contractions
• FHR changes resolves in 3-10 min spontaneously
• If not resolved in 15 min : Suspect AP/NR-FHR
43
44. RENAL FAILURE
Etiology : Renal or Prerenal
Diagnosis : S Cr X 3.0, or UO < 300 mL/ for 24
hours
Commonly complicated by volume overload/
hyponatremia/hyperkalemia/hypocalcemia/metabolic
acidosis.
Commonly presented with thirst/hypotension/
tachycardia/reduced JVP/dry mucus membrane/
reduced axillary sweating
Sp.Inv. : Serum Urea, Creatinine, Urinary Na+,/urine
Osmolality/ Urinay Cast
44
45. IP/OP charting daily
Input = Output/24hrs + 500ml(non
febrile)+ 200 ml/ deg C of inc. in Temp
No hypotonic fluid
Isotonic fluid to be fluid of choice
FCT :1000 ml of isotonic fluid over 1 hr
No UO increases, further
UO increases, maintain
infusion will be guarded
at 100 ml/hr
by CVP/PWP
Protein intake of 0.6 g per kg per day
45
46. Hyperkalemia, should be treated by
1) Decreasing intake
2) Controlling intracellular Shifts
Dialysis
a) Hemodialysis : Hemodynamically Stable patients &
following abdominal Surgery(LSCS)
b) Peritoneal Dialysis : Hemodynamically Unstable
patients
Acidosis- 5% Sod. Bicarbonate if S. HCO-3 > 15
mmol/L or arterial PH < 7.2
46
47. Indication of Dialysis.
-Clinical evidence of Uremia
-Intractable intravascular overload
-Hyperkalemia resistant to conservative tr.
-Serum Creatinine > 8 mg/dl
Coagulopathy : FFP for a prolonged aPTT,
Cryoprecipitate : Fibrinogen < 100 mg/dL,
Platelets Transfusion : TPC < 20,000/mm3
Continuous AV hemodiafiltration(CAVH)
Continous Venoveno hemodiafiltration(CVVH)
47
48. HELLP SYNDROME
• LOUIS WEINSTEIN (1982)
• 0.3% of all Pregnancies
• 20% of Severe Preeclampsia & Eclampsia
• Delivery is the only cure
• More common in white women.
• 2/3rd : Antepartum & 1/3rd : Postpartum(48hr)
48
49. a) Biomarkers to follow disease progression : Platelet
Count & Serum LDH, HCG,Maternal AFP,Serum
Haptoglobin
• Rate of recurrence in subsequent pregnancy : 2-19%
• Manifested by nausea, vomiting, epigastric pain, and
biochemical and hematological changes.
• Two Clinical Types :
1) Full HELLP syndrome : Considered for
delivery within 48 hours
2) Partial HELLP Syndrome : Candidates for
more conservative management
49
50. TYPES & DIAGNOSIS
• Class 1 – TPC <50 Hemolysis
000/mm3. 1) Abnormal Peripherical Smear
• Class 2 – TPC: 50 000 - 2) Serum Bilirubin >1.2 mg/dl
100 000/mm3. Elevated Liver Enzymes
• Class 3 – TPC :100 a) SGOT/SGPT >72 UI / L
000-150 000/mm3.
b) LDH >600 UI / L
Low Platelets
Platelet Count < 150 103 /mm3
50
54. MANAGEMENT
• Bed rest
• Fluid : Crystalloid /Albumin-5 to 25%
• Magnesium Sulphate
• Antihypertensive
• Volume Expansion & Electrolyte Balance
• Corticosteroids: Dex/Pred/Beta(10/10/5/5)
• Surveillance
a) Maternal : BP/Lab Invest./Hemodynamic Monitoring
b) Fetal : FHR & BPP
• Transferring patient to ICU where safe delivery can be
done
54
55. • Indication for termination
a) GA 32-34 weeks
b) Bleeding/DIC
c) Abruptio Placentae
d) Eclampsia
e) Abnormal FHR pattern
• Antithrombotics : Low dose Aspirin &
Heparin
• Steroid : HELLP syndrome with TPC <
100,000 per mm3
55
56. ADMINSTRATION
OF CORTICOSTEROIDS
Improves Maternal Outcome
1) Improves thrombocyte count
2) Improves Urine Output
Improves Perinatal Outcome
a) Improves Pulmonary Maturity
b) Decreases IVH
c) Decreasing Necrotising Enterocolitis
56
57. Continue till Liver function abnormalities are resolving
and TPC > 100,000 per mm3
HELLP Syndrome : Prophylactically with magnesium
sulfate to prevent seizures
Absence of improvement of the thrombocytopenia
within 72-96 hrs Postpartum : MOF.
Patients with DIC should be given fresh frozen plasma
and packed red blood cells.
57
58. MANAGEMENT OF LABOR
If transabdominal delivery is required, prefer :
a) Vertical Skin Incision.
b) Corporeal incision of the uterus .
c) SD of Placenta to avoid hemorrhage
Admisión in Obstetric ICU until:
(1) Sustained of TPC and a in LDH.
(2) Diuresis : UO <100ml/h X 2 hours .
(3) Control BP with SBP 150 mm Hg & DBP < 100
mm Hg.
58
59. MANAGEMENT OF LSCS
GA : Platelet count <
75000/cmm
Transfuse 6 Packs of
platelet if < 40000/cmm
Insert Subfascial drain
Secondary Skin Closure or
leave
Observe for bleeding from
Upper abdomen before
closure
59
60. INTRACRANIAL HEMORRHAGE
• 5% presented with focal neurological deficits.
• Gross hemorrhage is due to ruptured arteries
caused by severe hypertension.
• Eclampsia : Loss of Cerebral auto-regulation ,
hyper-perfusion similar to hypertensive
encephalopathy
• Cerebral edema in 95-100% cases of Eclampsia
60
61. Widespread edema, ischemia,thrombosis .
CT : Hypodense area in Cortex , corresponds to
Petechial hemorrhage and infarctions
Remarkable changes in area of distribution of
Posterior Cerebral A.
MRI : Hyperperfusion due to Vasogenic Edema
Eclampsia : 25% were area of infarction
Intracranial bleeding is leading cause of mortality
61
62. Autopsy Specimen from a 40-Year-Old Woman with Eclampsia
and Subarachnoid Hemorrhage
Greene M. N Engl J Med 2003;348:275-276
62
63. Conservative
1) Low Dose Aspirin : 30-100 mg/day
2) Anticoagulant :Conventional Heparin/LMW Heparin
3) Thrombolytics : Heparin/ Stretokinase/ Alteplase/
Urokinase
4) Antihypertensives
5) Mannitol(20%) :1 g /kg 20% solution IV 8 hrly
6) Glycerol : 30 ml 6hrly orally
7) Dexamethasone : 10 mg IV followed by 4 mg 6hrly
Surgical
1) Bore-Hole Aspiration
2) Decompression
63
64. DIC MANAGEMENT
• 7-10 % of patients with eclampsia
• DIC is defined as presence of thrombocytopenia,
low fibrinogen(<300 mg/dl) & FDP >40 mg/dl
• Two forms : Acute & Chronic or Overt & Nonovert
• Two Stages : Hyper & hypocoagulable
• Central pathology : Progressive generation of
thrombin in blood due to TF in underlying
pathology
• Common specific investigations : PT /aPT /TPC
/Fibrinogen/D-Dimer or FSP/Antithrombin/ PS/
thrombelastography
64
65. • Cardinal rule in treatment of DIC is to identify &
treat underlying cause.
Nonspecific
Airway management
Restoration of blood volume
- Fresh Plasma/Fresh Frozen Plasma
- Platelet Concentration
- Cryopreciptate
Adequate oxygen delivery
CPV monitoring
Ionotropes
Correction of Electrolyte imbalance
65
66. PLATELET TRANSFUSION
Dose : 1 U / every 10 kg
Weight.
Spontaneous Bleeding : TPC <
50.000/mm3.
In PP Period, maintain the
Count
a) >50.000/mm3 LSCS
b) >20.000/ mm3 VD Each pack is 40-
Dexamethasone : HELLP & 50 ml raises
Sev. thrombocytopenia . count by 7500-
Alternatives : Plasmaphersis & 10000/cmm
Immunoglobulins 66
67. FOZEN PLASMA/FFP
• Each bag=1Unit containing 100-
600 ml
• Contains all procoagulant factors
including labile factor
• 1U FFP=2U of Frozen Plasma
• Dose : 10-15ml/kg(both)
• Infuse over 2-3 hr
• Infuse < 4 hrs of issue
• Each bag raises factors by 25%
FFP
67
68. Specific :
1) Heparin : Conventional/LMW
2) Fibrinogen Conc.
3) Antifibrinolytics
4) Thrombodulin
5) Activated Factor VII
6) Antithrombin Conc.
7) Activated Protein C(APC)
8) Recomb. TF pathway inhibitor : Tifacogin
9) Gabexate Mesylate : Syntheic inhibitor of serine
proteases such as thrombin & anticoagulant activity
in absence of antithrombin
68
70. • Titrate Insp. Oxygen Conc. against SpO2
• Head tilt/Sit up Position
• 100%-Oxygen Inhalation
• Restricted Fluid intake
• Intubate if necessary
• Mechanical Ventilation with CPAP
• Evaluate for underlying etiology
• Drug therapy :
1) Inj Frusemide 40 mg IV 20 mg Mannitol
2) IV Aminophylline (if bronchospasm)
70
71. MORTALITY
&
MORBIDITY
• Maternal : 8-36% most frequently related to
seizure activity
• Fetal : 13-30% most frequently related to
iatrogenic prematurity
71
72. FOLLOW UP
Postnatal follow up for 6 weeks
Persistence of HTN > 12 weeks : Medical evaluation
Recurrence risk
1) Onset at term : 30%
2) Onset at 30-37 weeks : 40%
3) Onset at < 30 weeks : 70%
Permanent Neural Damage
Increased risk of Essential Hypertension
Contraception :
a) POP or Low dose Pill
b) No Puerperal tubal ligation 72
73. PREVENTION
Primary : Prevention of development of preeclampsia
• Folic Acid & Calcium Supplentatation
• Fish oil capsules : Modify abnormal PG balance
Periodic Monitoring BP & Weight gain
Antioxidants
• Reduced endothelial cell activation , reduction in
preeclampsia
a) Vit-C 1000 mg/day
b) Vit-E 400 mg/day
73
74. • Periodic Screening :
a) Serum Uric Acid > 6.0 mg/dl
b) Doppler :Uterine Artery & Umibilical Vein in 2nd
trimester.
c) Biophysical Testing
d) Ultrasonography 4 Weekly
e) Roll Over Test at 28-32 Weeks
f) Platelet Count(High Platelet Volume)
g) Urinary Calcium < 12 mg/dl
h) Serum Fibronectin
i) Urinary Protein
j) Serum Antithrombin-III
k) Fetal DNA in maternal Serum 74
75. EnSuRing good
exercise
during
pregnncy
To prevent one case of Eclampsia
- 71 women with Preeclampsia need to be treated
- 36 women with imminent eclamspia need to be treated
- 129 women without symptoms(Gest.Hypertension)
75
76. Secondary : Pharmacological agents to prevent
convulsion in preeclampsia
1) Salt restriction
2) Inappropriate diuretic therapy
3) Low dose aspirin (60mg)/Baby Aspirin
4) Magnesium Sulphate
5) Antihypertensives
Tertiary : Preventing subsequent convulsion in
established eclampsia.
With optimum Mode of management
we can prevent 70% of eclampsia
76