Pre-Eclampsia New challenges for the Anaesthetist

OAA 3 day Course

Church House Westminster

7/11/2012

Chris Elton Consultant in Obstetric Anaesthesia

Leicester Royal Infirmary

University Hospitals of Leicester NHS Trust

Declarations

• Margaret Thatcher paid for my university

education (and others of my generation)

• Edwards (Flotrac) took me to Geneva and

fed me once

• Sonosite keep making me look efficient

nihil novi sub sole Ecclesiastes 1:9

“New” Challenges

• Maternal Mortality

• What anaesthetic for Caesarean Section? – How should I manage general anaesthesia?

– How should I manage regional anaesthesia?

• HELLP?

Saving Mothers Report (2005-

2007)

• 622 Deaths

• 334 Due to eclampsia – CVA

– Cardiac failure/Pulmonary oedema

• Delay – in seeking help

– in transportation

– in referral

• Action – Provision (and acceptance) of antenatal care

– Detection of preeclampsia

– Training of Health Professionals

South Africa

• Population 50 million (UK 69 million)

• 1.2 million square kilometres (UK 242,000)

• GDP $338.7 billion (28th)

• Inflation 4.27%

• Growth1.43%

• Unemployment 23.8%

Case 1 • Well Normotensive Post Term Induction-Delayed

• BP check 170/90

• CTG decelerations

• EmCS BP 200/105

• STP/Sux/RSI/ETT

• BP 195-210/

• Deliver baby

• “Failure to wake up”

• Massive Intracranial Haemaorhage (Intrahepatic)

• Death

CEMACH 2002-5

CEMACH (CEMACE)-2002-2005

CEMACE-2005-2008

CEMD-Specific Anaesthesia

Related • 1994-96

– “a rather large dose of thiopentone was given…presumably because her blood pressure was so high at induction. Magnesium infusion was continued…she died five days after delivery….with fulminant hepatic failure”

– “general anaesthesia for foetal distress..routine general anaesthetic…a large inoperable intracerebral haematoma….brain stem death was diagnosed”

• 1997-99 – “The largest single cause of death….was intracranial haemorrhage-reflecting

a failure of antihypertensive treatment”

– “An emergency caesarean section was performed under general anaesthesia. At induction of anaesthesia, the woman’s blood pressure was 250/160”

• 2000-2002 – “her blood pressure rose to 215/120…..A caesarean section was

performed....after delivery. She developed twitching, slurred speech and mouth dropping…..a massive intracranial haemorrhage….HELLP syndrome”

– “had a seizure…blood pressure 150/100..proteinuria +++…hydralazine and magnesium sulphate and underwent caesarean section for fetal distress.. After delivery …170/115…180/120..(HELLP)..intracranial haemorrhage.”

The Pressor Response to

Intubation

• “Twenty patients with severe

pregnancy induced (PIH) or pregnancy

aggravated (PAH) hypertension,

undergoing general anaesthesia for

Caesarean section were studied. All

patients received a standard

anaesthetic technique designed to

control the potentially dangerous,

reflex cardiovascular instability

associated with laryngoscopy”

• The average increase in systolic arterial

pressure (SAP) was 56.4 mm Hg following

laryngoscopy and tracheal intubation. “

• Connell et al BJA 1987, 59 1375-1380,

Cerebral Circulation & GA

Ramanathan Anesth Analg 1999 88 357-361

Control of BP at Induction

The Fragile Circulation

General Anaesthesia • Stabilise Patient

• Do not risk Maternal Death to “save” Fetus • Airway Assessment

• Hypoxaemia-more likely/more harmful

• Laryngeal oedema (intubation and extubation).

– Hoarse voice

• Consider IBP • STP/Sux/O2/N2O/Isoflurane

• Pressor response – MgSO4 2-6g

– Alfentanil 1-2mg

– Remifentanil 0.5ug/kg (Glycopyrolate)

– Fentanyl 1.5-5ug/kg

– Lignocaine 1-2mg/kg

– Labetolol 20mg

– Hydralazine

– Esmolol 0.5-1.5mg/kg

– GTN

Technique used by UK

Anaesthetists (April 2002) -Attenuating the Pressor Response

Wight and Bythell IJOA 2003 12 228

Alfentanil

Labetolol

Magnesium

FentanylRemifentanil

General Anaesthesia

• Care with muscle relaxants and Mg- test TOF

• Extubation

• Esmolol/Lignocaine

• Leak

• Consider ICU/HDU • 24 -72hrs+

• Analgesia

• Thromboprophylaxis • TEDS, Flowtron, Mobilisation

• LMWH -Give unless significant bleeding risk

Case 2

• Friday afternoon

• 30/52

• New Hypertension

• Proteinurea

• In hospital 2 weeks

• “Reverse end diastolic flows”

• Caesarean Section

Technique used by UK

Anaesthetists (April 2002) Wight and Bythell IJOA 2003 12 228

Spinal

CSE

Epidural

General

Anaesthesia

• Regional

– Epidural

– Spinal

– CSE

– Modified/Sequential CSE

• GA only if regional contraindicated

– Regional Possible even after “stable” Eclampsia

• CONSIDER IBP

Haematological considerations

• Coagulopathy in Preeclampsia

• Thrombocytopaenia

• Deranged clotting

• Fibrinolysis

• Considerations

• Any evidence of DIC?

• Any abnormal bleeding?

• Stability of platelet count

Thrombocytopaenia-how low?

• Coagulation measured by TEG • Abnormal <66 Orlikowski BJA 1996 77 157-61

• Normal >75 Sharma Anesthesiology 1999 90 385-90: Anesth and Analg 1997 85 385

• Platelet count of < 75 predicts abnormal bleeding time • McDonagh Canadian JA 2001 48 563

• Spinal haematoma with platelets 71

• Yuen Anaesthesia 54 350-71

• Spinal haematoma with normal platelets, (slightly) raised FDP’s, prolonged APTT

• Lao Canadian JA 1993 40 340

• Spontaneous Haematoma

• Doblar, Schumacher IJOA 2005 14 256-260

• UK anaesthetists choose platelet count >80 • Wight and Bythell IJOA 2003 12 228

Sharma: Anesthesiology, Volume 90(2).February 1999.385-390

Spinal subarachnoid hematoma following spinal

anesthesia in a patient with HELLP syndrome

Koyama et al 2010 IJOA 87-91

Which Regional for LSCS?

• Traditional teaching favours epidural

• BUT

• Pre-eclamptics experience less hypotension with spinal anaesthesia than non pre-eclamptics and require less ephedrine

• In preeclampsia spinal anaesthesia causes no more hypotension than epidural anaesthesia

• Epidural anaesthesia doesn’t work well!

Spinal Hypotension in PET

Aya A et al. Anesthesia and Analgesia 2003 97 867-72

Aya A et al. Anesthesia and Analgesia 2005 101 869-75

Ephedrine Requirements and PET

• 20 Preeclampsia

• 20 Normotensive

• 2.5ml heavy Marcain Fentanyl 12.5mcg

• 20% Systolic Baseline Ephedrine dose 6mg

• 16.4 mg vs 27.9mg

• Clark, Sharwood-Smith,

Stewart IJOA 2005 14 9-13

Wallace DH Obstetrics and Gynecology 1995; 86 277-84 Hood Anesthesiology 1999; 76 616-20

Spinal vs Epidural

• Visalyaputra S et al Anesthesia and Analgesia 2005 101 862-868

• “Large” Prospective, Randomized, Multicentre Study

• Hydroxyethylstarch 500ml

• Epidural Lignicaine/Adrenaline/Fentanyl (Morphine) Spinal

Bupivacaine (11mg)/Morphine (0.2mg)

• BP every minute for 20 mins; every 2 mins for 10 min

• 5 patients in epidural group converted to GA (pain)

Epidural n=47 Spinal n=53

Hypotension <1min

(SAP<100mm Hg) 11 27

No Hypotension 36 26

Visalyaputra et al Anesthesia and Analgesia 2005 101 862-8

Santos, Birnbach Anesthesia and Analgesia 2005 101 859-61

Cardiac Output

Maternal Central Hemodynamics inHypertensive Disorders of Pregnancy

PAUL M. BOSIO, MD, PETER J. MCKENNA, MD, RONAN CONROY, AND

COLM O’HERLIHY, MD

Objective: To document maternal central hemodynamics

during the preclinical and clinical phases of nonproteinuric

gestational hypertension and preeclampsia.

Methods: We conducted a longitudinal study of 400 primi-

gravidas who were monitored throughout pregnancy using

Doppler echocardiography. Multinomial logistic regression

was used to identify variables associated with risk of hyper-

tension.

Results: Gestational hypertension developed in 24 women

and preeclampsia developed in 20. Compared with normo-

tensive controls, women who had preeclampsia had signif-

icantly elevated cardiac outputs before clinical diagnosis,

but total peripheral resistance was not significantly different

during this latent phase. During the clinical phase of pre-

eclampsia, there was a marked reduction in cardiac output

and increase in peripheral resistance. All women who had

gestational hypertension had significantly elevated cardiac

outputs before and during the clinical course of the condition.

Conclusion: Our data support the concept of a hyperdy-

namic disease model for preeclampsia, with a subsequent

hemodynamic crossover to low cardiac output and high

resistance circulation coinciding with the onset of the clini-

cal syndrome. Women with gestational hypertension had no

such hemodynamic crossover and maintained hyperdy-

namic circulation throughout pregnancy. (Obstet Gynecol

1999;94:978 –84. © 1999 by The American College of Obste-

tricians and Gynecologists.)

A severe disturbance of the normal physiologic hemo-dynamic homeostasis of pregnancy occurs during pre-eclampsia, but the nature of this disturbance is notcertain. Several studies described central hemodynam-ics during advanced preeclampsia, but most of them are

cross-sectional and reported conflicting findings, from

the traditional view that it is a vasoconstricted hypo-

perfusion disorder to the view that it is a low peripheral

resistance, high cardiac output state.1–4 Much of the

data are confounded by the fact that preeclamptic

patients have different severity and duration of the

disease and had different clinical treatment before he-

modynamic monitoring. Hemodynamic profiles at

study entry have been shown to vary widely in previ-

ously treated patients.1,5 In addition, reported cross-

sectional investigations of cohorts of mixed parity with

coexistent medical problems have contributed to the

disparity of findings.

By contrast, hemodynamic investigations during the

latent phase of preeclampsia are scarce. In the longitu-

dinal study of Easterling et al,6 cardiac output was

consistently higher during the latent and clinical stages

of the disease in 9 subjects in whom preeclampsia

developed. Visser and Wallenburg,5 on the other hand,

reported that their preeclamptic patients were charac-

terized by a uniform pattern of low cardiac index and

high systemic vascular resistance before treatment.

A hypothetical disease model characterized by uni-

form vasoconstriction and hypoperfusion throughout

the latent and clinical phases of preeclampsia is not

consistent with much of the existing data. This discrep-

ancy suggests that the hemodynamic features of the

disease are more complex than originally postulated

and could also change during the evolution of the

pathophysiologic process. Once the condition has be-

come clinically evident cross-sectional studies are un-

likely to provide meaningful information about the

nature of the disease in early pregnancy. Our objective

was to clarify the evolution of this dynamic circulatory

disease by using noninvasive hemodynamic monitoring

in a large prospective study commencing in early

pregnancy, before the clinical signs of preeclampsia are

apparent.

From the Departments of Obstetrics & Gynaecology and Epidemiology& Biostatistics, Rotunda Hospital, Royal College of Surgeons in Ireland,and University College Dublin, Dublin, Ireland.The authors thank Declan Sugrue, MD, and Hugh McCann, MD,

consultant cardiologists, Mater Private Hospital, for their advice andtechnical supervision.This work was funded by a Friends of the Rotunda Research Grant and

The Monkstown Hospital Research Foundation.

978 0029-7844/ 99/ $20.00 Obstetrics & GynecologyPII S0029-7844(99)00430-5

Maternal Central Hemodynamics inHypertensive Disorders of Pregnancy

PAUL M. BOSIO, MD, PETER J. MCKENNA, MD, RONAN CONROY, AND

COLM O’HERLIHY, MD

Objective: To document maternal central hemodynamics

during the preclinical and clinical phases of nonproteinuric

gestational hypertension and preeclampsia.

Methods: We conducted a longitudinal study of 400 primi-

gravidas who were monitored throughout pregnancy using

Doppler echocardiography. Multinomial logistic regression

was used to identify variables associated with risk of hyper-

tension.

Results: Gestational hypertension developed in 24 women

and preeclampsia developed in 20. Compared with normo-

tensive controls, women who had preeclampsia had signif-

icantly elevated cardiac outputs before clinical diagnosis,

but total peripheral resistance was not significantly different

during this latent phase. During the clinical phase of pre-

eclampsia, there was a marked reduction in cardiac output

and increase in peripheral resistance. All women who had

gestational hypertension had significantly elevated cardiac

outputs before and during the clinical course of the condition.

Conclusion: Our data support the concept of a hyperdy-

namic disease model for preeclampsia, with a subsequent

hemodynamic crossover to low cardiac output and high

resistance circulation coinciding with the onset of the clini-

cal syndrome. Women with gestational hypertension had no

such hemodynamic crossover and maintained hyperdy-

namic circulation throughout pregnancy. (Obstet Gynecol

1999;94:978 –84. © 1999 by The American College of Obste-

tricians and Gynecologists.)

A severe disturbance of the normal physiologic hemo-

dynamic homeostasis of pregnancy occurs during pre-eclampsia, but the nature of this disturbance is not

certain. Several studies described central hemodynam-ics during advanced preeclampsia, but most of them are

cross-sectional and reported conflicting findings, from

the traditional view that it is a vasoconstricted hypo-

perfusion disorder to the view that it is a low peripheral

resistance, high cardiac output state.1–4 Much of the

data are confounded by the fact that preeclamptic

patients have different severity and duration of the

disease and had different clinical treatment before he-

modynamic monitoring. Hemodynamic profiles at

study entry have been shown to vary widely in previ-

ously treated patients.1,5 In addition, reported cross-

sectional investigations of cohorts of mixed parity with

coexistent medical problems have contributed to the

disparity of findings.

By contrast, hemodynamic investigations during the

latent phase of preeclampsia are scarce. In the longitu-

dinal study of Easterling et al,6 cardiac output was

consistently higher during the latent and clinical stages

of the disease in 9 subjects in whom preeclampsia

developed. Visser and Wallenburg,5 on the other hand,

reported that their preeclamptic patients were charac-

terized by a uniform pattern of low cardiac index and

high systemic vascular resistance before treatment.

A hypothetical disease model characterized by uni-

form vasoconstriction and hypoperfusion throughout

the latent and clinical phases of preeclampsia is not

consistent with much of the existing data. This discrep-

ancy suggests that the hemodynamic features of the

disease are more complex than originally postulated

and could also change during the evolution of the

pathophysiologic process. Once the condition has be-

come clinically evident cross-sectional studies are un-

likely to provide meaningful information about the

nature of the disease in early pregnancy. Our objective

was to clarify the evolution of this dynamic circulatory

disease by using noninvasive hemodynamic monitoring

in a large prospective study commencing in early

pregnancy, before the clinical signs of preeclampsia are

apparent.

From the Departments of Obstetrics &Gynaecology and Epidemiology& Biostatistics, Rotunda Hospital, Royal College of Surgeons in Ireland,and University College Dublin, Dublin, Ireland.The authors thank Declan Sugrue, MD, and Hugh McCann, MD,

consultant cardiologists, Mater Private Hospital, for their advice andtechnical supervision.This work was funded by a Friends of the Rotunda Research Grant and

The Monkstown Hospital Research Foundation.

978 0029-7844/ 99/ $20.00 Obstetrics & GynecologyPII S0029-7844(99)00430-5

CVP monitoring?

• Inaccuracy of CVP lines in preeclampsia

well established

• May only be useful if CVP is low (<4mmHg

• Associated with deaths in CEMD reports

• Large fluid shifts post partum particularly

dangerous with renal dysfunction

• UK anesthetists rate CVP monitoring of

limited use • Central venous pressure monitoring in severe preeclampsia: a survey of UK

practice.2011 M.W.M. Rucklidge, R.D. IJOA 370

Treating Hypotension

• Phenylephrine is the vasopressor of choice for prevention of spinal hypotension

• What is hypotension in preeclampsia? – SBP<100/120mmHg; MAP 10%/20%/30%<baseline?

• “more sensitive to vasopressors” – Beta blockers/Vasodilator therapy

• Most studies have used ephedrine

• Phenylephrine probably safe (but some authors consider it a contraindication)

Vallejo and Ramanathan. IJOA 2003 12 243-5

McKinlay and Lyons IJOA 2002 11 117-21

Phenylephrine-Fetal Effects

General Anaesthesia vs Spinal with

Fetal Distress Dyer et al Anesthesiology 2003 99 561-9

• Seventy patients randomised to GA or SAB

• “Non reassuring” fetal heart trace

• Neonatal indicators worse in SAB group

GA SAB

Neonatal

umbilical BE

4.68 +/- 3.3 7.13 +/- 4.0

Umbilical pH 7.23 7.20

Case 3

• 34 week home monitoring

• IUGR, Increasing BP despite treatment

• Absent diastolic flows –Reverse

• Induced

• Fitting...............

Eclampsia

• TREATMENT OF ECLAMPSIA IS MgSO4

– not phenytoin

– not diazepam The Eclampsia Trial Collaborative Group Lancet 1995; 345: 1455-63

• 5 per 10,000 deliveries: Mortality 1.8% (UK)

• Prophylaxis?

Prophylaxis of Eclampsia? Magpie (2002 Lancet 359 1877-1890)

• International Study 10,141 women

• Magnesium Sulphate Group – Fewer Seizures (0.8% vs 1.9%)

– More Side Effects (24% vs 5%)

– Lower maternal mortality (p=0.11) – Only in developing countries

– Not due to eclampsia

– Number needed to treat 91 • Severe PET 63

• Not severe PET 109

• Severe PET (25% of total) benefit most

• Definite benefits to developing countries

• All patients with severe PET and strong recommendation in those with moderate requiring antihypertensives should receive Magnesium

• 4g bolus 1g/hr reduce if oliguria/high creatine.

• Regularly check reflexes. Levels controversial

Case 4

• 27/52

• BP 150/100-expectant management

• Oligohydramnios, small baby

• Worsening BP despite treatment

• Epigastric pain, vomiting, headache

• Platelets 150, ALT 64, proteinuria

• Platelets 74, ALT 150, r time 13min

• Emergency CS (GA),Blood, Cryo, FFP

platelets

Case 4

• Hypotensive

• Low Hb

• Worsening clotting

• Shoulder tip pain

• CT/US

• Free fluid +

• Laparotomy

• Partial rupture SC

haematoma

• Packed

• Good Outcome (PTSD)

Subcapsular haematoma

• Rare complication of late

pregnancy/early puerperium

• Marsh et al (2003)1 - 150 cases

published

• Triad of

– Pre-eclampsia

– RUQ pain

– Acute hypotension

• Mortality with rupture >60%

• Awareness and early diagnosis

reduce mortality

• Pathogenesis

– Periportal haemorrhagic

necrosis, coagulopathy and

hypertension

– Haematoma may rupture

spontaneously or secondary to

trivial trauma

• Investigations

– US: quickest

– CT: sensitive

– MRI

1) Marsh FA, Kaufmann SJ, Bhabra K, Surviving hepatic rupture in

pregnancy – a literature review with an illustrative case report. J Obs

Gynae 2003; 23:109-13

Subcapsular haematoma

• Conservative

• Surgical

– haemodynamically unstable

– documented expansion of capsule

– laparotomy2 with hepatic packing

– hepatic artery ligation or embolisation

– argon beam coagulator in hepatic rupture

• Liver transplantation in uncontrolled bleeding or severe hepatic necrosis

2) Poo JL, Gongora J. Hepat haematoma and rupture in pregnancy. Ann Hepatol 2006; 5:2224-6

HELLP

• Elevated Liver enzymes, defined as: • Serum aspartate aminotransferase (AST) ≥70 U/L

• OR

• Gamma-glutamyltransferase (γ-GT) ≥70 U/L

• OR

• Alanine aminotransferase (ALT) ≥70 U/L

• AND

• Low Platelets, defined as platelet count < 100 x109/l. • AND EITHER

• Haemolysis, • abnormal peripheral blood smear

• LDH levels ≥600 U/L

• bilirubin ≥20.5 µmol/l

• OR

• Hypertension, • systolic ≥ 140 mmHg or a diastolic ≥ 90 mmHg

• OR

• Proteinuria, • 1+ (0.3 g/l) protein:creatinine, ratio of 30 mg/mmol, urine protein 300 mg or more per 24 h

Pulmonary Oedema

“Often too many persons become involved in treatment without appropriate co-ordination, leading to inadvertent fluid overload and (the) serious problems”

• Incidence 2.9% in US

• Increased frequency in older multigravid • Sibai 1987 AJOG 156 1174-9

• 2.3% in UK (25/1087)

• 70% occurs post partum

• Associated with fluid challenge in response to oliguria

• Renal failure (dialysis 0.55%) • Tuffnell et al BJOG 112 875-80

Acute Renal Failure

Renal

Failure

Dialysed

Robson (1999) 5/324 2/324

Sibai (1990) 18/1684 9/1684

Tuffnell (2005) 6/1087)

Haddad (Sibai)

HELLP(2000)

9/183

Sibai (1993)

(HELLP)

33/442

Conclusion

• Maternal Mortality of PET is still high in

many parts of the world

• Obtund the pressor response to intubation

• Spinal Anaesthesia is a resonable choice

for CS-but prepare to be surprised

• Syntocinon may cause significant

problems

• HELLP is a significant cause of morbidity