Pre-eclampsia -New challenges for the Anaesthetist

OAA 3 day course

Church house Westminster 9/11/11

Chris Elton Consultant in Obstetric Anaesthesia

Leicester Royal Infirmary University Hospitals of Leicester NHS Trust

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 spinal anaesthesia? – How should I manage epidural anaesthesia?

•  Eclampsia

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

Saving Mothers Report (2005-2007)

•  20.1% increase in deaths

•  AIDS (43.7%) •  Hypertension (15.7%) •  Haemorrhage (12.4%) •  Sepsis (9.0%) •  Pre-existing maternal disease (6.0%).

South Africa

•  Population 50 million (UK 69 million) •  1.2 million square kilometres (UK 242,000) •  GDP $338.7 (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 Haemorrhage (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

Emergencies for Single Organ Doctors (SODS)

•  Obstetric “ABC” – Assess the vagina/cervix

– Bleep the Anaesthetist

– Caesarean Section (GA)

•  Anaesthetic “ABC” – Assess the patient – Bring the blood pressure down (<160) – Cautiously induce anaesthesia

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 •  Proteinuria •  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 does not 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 Lignocaine/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

inserted in a radial artery after local skin infiltrationwith lidocaine. In addition to continuous invasive bloodpressure monitoring, we used the LiDCOplus monitor(LiDCO Ltd., Cambridge, UK) which provided contin-uous haemodynamic measurements of stroke volume(SV), CO and SVR.9 None of the patients had a centralvenous catheter, and a central venous pressure (CVP) of5 mmHg was assumed for the calculation of SVR.

Preeclamptic patients received spinal anaesthesia forcaesarean section. The intrathecal dose of isobaricbupivacaine was not standardised, but individualizedaccording to height, weight and gestational age. Anintravenous crystalloid infusion was started concur-rently with spinal anaesthesia and a 5 IU bolus of oxy-tocin was administered after delivery of the baby.

Haemodynamic data were stored in the LiDCOplus-monitor and downloaded as csv-files (text-files) for eachpatient. Construction of the data set was done usingMatLab version R2007a (The MathWorks, Natick,MA). The baseline was defined as the mean of 30 s be-fore oxytocin was given. Extreme values identified asartefact/noise were removed from the dataset. All datawere analyzed in SPSS statistical program version 16.0(Statistical Package for Social Sciences Inc., Chicago,IL) using the independent samples t test.

Results

Eighteen women with severe preeclampsia were includedin this observational study. Maternal characteristics arepresented in Table 1. Three patients had previous preg-nancies with preeclampsia. Three patients had diabetesmellitus and were on insulin therapy. All but one patienthad symptoms such as headache, visual disturbances,dyspnoea, or epigastric pain; two patients had HELLPsyndrome. Sixteen patients received labetolol beforedelivery and 12 were treated with MgSO4. The meanbupivacaine dose for spinal anaesthesia was 10.6 mgwith the addition of sufentanil (4–5 lg) or fentanyl(10–25 lg). Nine patients had an intravenous phenyl-ephrine infusion started simultaneously with spinal

anaesthesia. Baseline haemodynamic values beforespinal anaesthesia are presented in Table 2.

All 18 patients were given 5 IU of oxytocin. All pa-tients had a decrease in SAP and SVR after oxytocin,and all had a compensatory increase in heart rate (Ta-ble 2 and Fig. 1). Five of the patients had a decreasein CO due to a decrease in SV.

Discussion

This observational study describes the haemodynamicfindings in 18 women with severe preeclampsia in clini-cal practice, demonstrating the heterogenous responseto oxytocin within this group of patients. Whilst a de-crease in SAP and SVR was observed in all patients, fivehad a decrease in CO after oxytocin. All patients had anincrease in heart rate (HR), and the decrease in CO inthe five patients was due to a decrease in SV.

Baseline haemodynamic values in our preeclampticpatients were similar to the findings of Dyer et al.8 Base-line CO and SVR demonstrate the heterogeneityamongst those with severe preeclampsia. The haemody-namic effects following a 2.5-IU bolus of oxytocin usedin Dyer’s study also differed in their patients, showing aminor increase in SV. None had a decrease in COalthough one patient demonstrated no increase in CO.This indicates that lowering the oxytocin dose resultsin less haemodynamic instability, and we recommendgiving a lower dose of 0.5–1 IU oxytocin to preeclampticwomen.10,11

Comparing the 18 preeclamptic patients given 5 IUoxytocin to healthy patients given the same dose, thepreeclamptic patients had a much smaller increase inCO, SV, and HR. All 80 healthy pregnant women, in-cluded in another study during the same time period,had an increase in cardiac output.7 In contrast, five ofthe preeclamptic patients had a decrease in CO. The rel-ative decrease in SAP after oxytocin was not differentbetween preeclamptic and healthy women. Thus, bloodpressure monitoring alone might not detect the haemo-dynamic differences between these groups.

Table 1 Maternal characteristics and drug therapy

Age (years) 32 [19–40]Gestation (weeks) 33 [26–38]Weight (kg) 93 [67–130]Height (cm) 168 [156–178]Body mass index (kg/m2) 33 [21–59]Nulliparous 13In vitro fertilisation pregnancy 5Essential hypertension 3HELLP syndrome 2U-protein/creatinine 421 [260–740]Blood loss (mL) 458 [150–900]

Data are mean [range] or number.

Table 2 Haemodynamic variables before spinal anaes-thesia and after oxytocin

Pre-spinal Change postoxytocin (%)

Cardiac output (L/min) 7.1 (1.2) +32 (46)Systolic arterial pressure

(mmHg)181 (20) !36 (10)

Mean arterial pressure(mmHg)

128 (15) !38 (7)

Systemic vascularresistance (dyns.s.cm!5)

1421 (315) !52 (13)

Stroke volume (mL) 82 (14) +6 (27)Heart rate (beats/min) 87 (12) +22 (19)

Data are mean (SD); Compared with values 30 s before oxytocinadministration.

E. Langesæter et al. 27

The effects of antihypertensive treatment in pre-eclamptic patients could explain some of the differencesin haemodynamic response to oxytocin in preeclampticas compared to healthy pregnant women, with a muchlesser cardiac compensation to oxytocin in preeclampticpatients. But it is difficult to explain why five patientswith severe preeclampsia were unable to increase SVand had a decrease in CO. Our findings could suggest adiastolic dysfunction in some women with severe pre-eclampsia; they might not be able to increase CO, SV,and HR in the same way as healthy pregnant women inresponse to the vasodilatory effect of oxytocin. Themuch reduced increase in SV in preeclampsia is an inter-esting finding. There are few publications on diastolicdysfunction in preeclamptic patients. Andrietti et al.12

found that women who had previously suffered with pre-eclampsia and had a low plasma volume (present in 30%)had persistent diastolic dysfunction. Aardenburg et al.13

demonstrated that women who had previously sufferedpreeclampsia with subnormal plasma volume were un-able to increase SV with moderate exercise. Further-more, Bamfo et al.14 found that preeclamptic women

had impairment in diastolic function due to both intrin-sic contractility and reduced diastolic filling. Our samplesize was small but our findings suggest that patients withpreeclampsia may have a more unpredictable response tooxytocin. A lower plasma volume could explain whysome women with preeclampsia cannot increase theirSV as a response to the vasodilatory effects of oxytocin.Whatever the cause of the variable haemodynamiceffects of oxytocin in preeclamptic patients, cliniciansshould be aware of the paradoxical effects of oxytocinin a large proportion of these patients.

In our view, patients with severe preeclampsia must betreated on an individual basis. In our department, an arte-rial line is routine during caesarean section in womenwithsevere preeclampsia, and we continue invasive monitor-ing postoperatively. The CO monitor used in this studyhas been validated in other patient groups,15,16 and therehave been recent reports of its use in pregnant wo-men.8,17,18 As we did not use a central venous catheter,CVP was given a value of 5 mmHg. This would not haveany important impact on the calculation of SVR, as CVPis much lower compared to mean arterial pressure.

0 10 20 30 40 50 60 70 80 90 1006

8

10Haemodynamic effects of oxytocin 5 units

CO

(L/m

in)

0 10 20 30 40 50 60 70 80 90 100600800

100012001400

SV

R(d

yns.

s.cm

!5)

0 10 20 30 40 50 60 70 80 90 100

120

140

160

SBP

(mm

Hg)

0 10 20 30 40 50 60 70 80 90 10070

80

90

100

SV (m

l)

0 10 20 30 40 50 60 70 80 90 100708090

100110

HR

Time (in seconds)

Fig. 1 The haemodynamic effects of 5 IU oxytocin in 18 patients with severe preeclampsia Oxytocin is given at time 0.

28 Haemodynamics in preeclampsia

ORIGINAL ARTICLE

Haemodynamic effects of oxytocin in women with severepreeclampsia

E. Langesæter, L.A. Rosseland, A. StubhaugDivision of Anaesthesia and Intensive Care Medicine, Oslo University Hospital – Rikshospitalet, Oslo, Norway

ABSTRACTBackground: Several previous publications demonstrate the significant haemodynamic effects of oxytocin in healthy pregnantwomen, but there is only one publication of the oxytocin effects in women with severe preeclampsia. We investigated the haemo-dynamic effects of oxytocin in women with severe preeclampsia using invasive haemodynamic monitoring.Methods: Eighteen women with severe preeclampsia were included in this observational study. All women had continuous invasivehaemodynamic monitoring during spinal anaesthesia for caesarean section using the LiDCOplus monitor. Preeclamptic patientswere given intravenous boluses of 5 IU oxytocin following delivery.Results: Following an intravenous bolus of 5 IU oxytocin all patients had an increase in heart rate, a decrease in systemic vascularresistance and a decrease in blood pressure. Five patients had a decrease in cardiac output due to an inability to increase strokevolume.Conclusions: The haemodynamic effects of oxytocin in women with severe preeclampsia may be less predictable compared to find-ings in healthy pregnant women, suggesting that oxytocin should be given with caution in women with severe preeclampsia.

!c 2010 Elsevier Ltd. All rights reserved.

Keywords: Severe preeclampsia; Neuraxial anaesthesia; Oxytocin; Cardiac output; Invasive monitoring; LiDCOplus

Introduction

Preeclampsia is a multi-system disease affecting 5–10%of pregnant women.1 The disorder can result in severecomplications including eclampsia, pulmonary oedema,HELLP (haemolysis, elevated liver enzymes, and lowplatelets) syndrome, or renal failure. Preeclampsia is amajor cause of maternal and neonatal morbidity andmortality. Although preeclamptic patients are oftenhypovolaemic with low cardiac output (CO) and in-creased systemic vascular resistance (SVR), this patientgroup is heterogeneous.2 Increased total vascular resis-tance, a high relative wall thickness of the left ventricleand a hypertrophied ventricle are independent predic-tors for developing maternal and fetal complications inpreeclamptic pregnancy.3

Oxytocin is a vasodilator acting on vascular endothe-lial receptors producing a calcium-dependent responsevia stimulation of the nitric oxide pathway.4 There areseveral publications on the haemodynamic effects ofoxytocin in healthy pregnant women,5–7 but only one

previous study showing its effects in severe preeclamp-sia.8 The aim of our observational study was to examinethe haemodynamic response to oxytocin in women withsevere preeclampsia.

Methods

Eighteen women with severe preeclampsia were includedin this study conducted at Oslo University Hospital,Rikshospitalet from August 2005 to August 2008 (regis-tered with clinicaltrials.gov: NCT00403572). The proto-col was approved by The Regional Medical ResearchEthics Committee for Southern Norway and womengave oral and written consent to participate. The onlyexclusion criterion was a contraindication to neuraxialanaesthesia.

Severe preeclampsia was defined as a systolic arterialpressure (SAP) P 160 mmHg with proteinuria, andeither headache, visual disturbance, dyspnoea or epigas-tric pain. Women with a SAP P 160 mmHg and symp-toms were given magnesium sulphate (MgSO4) 4 gintravenously as a loading dose, followed by an infusionof 1 g/h for 24 h.

After monitoring was established with electrocardi-ography and pulse oximetry, a 20-gauge cannula was

Accepted October 2010Correspondence to: Eldrid Langesæter, Division of Anaesthesia andIntensive Care Medicine, Oslo University Hospital – Rikshospitalet,N-0027 Oslo, Norway.E-mail address: eldrid.langesaeter@rikshospitalet.no

International Journal of Obstetric Anesthesia (2011) 20, 26–290959-289X/$ - see front matter !c 2010 Elsevier Ltd. All rights reserved.doi:10.1016/j.ijoa.2010.10.004

www.obstetanesthesia.com

was therefore reversed, with an RR ratio of 0.2 (95% CI0.1, 0.5).

Normal total peripheral resistance was associatedwith subsequent preeclampsia at 10–14 weeks, with anRR ratio of 0.8 (95% CI 0.6, 1.1) and mean value of 1082dynes ! sec ! cm!5 (P " .114). A normal peripheralresistance thereafter was maintained throughout thepreclinical course of pregnancy in these patients (Table2). A marked increase in total peripheral resistance wasobserved subsequently in these patients during theclinical course of preeclampsia. Thus, after 36 weeks’gestation, when all remaining patients were diagnosedas preeclamptic, a higher peripheral resistance wassignificantly associated with the condition (RR ratio 4.6,95% CI 2.3, 9.4), with a mean measurement of 1687dynes ! sec ! cm!5 (range 1383–2451, P # .001).

Figure 3 shows the measurements of cardiac outputand total peripheral resistance in individual womenwho had gestational hypertension plotted against the

entire cohort. High cardiac output was significantlyassociated with subsequent gestational hypertension asearly as 10–14 weeks’ gestation (RR ratio 1.9, 95% CI1.2, 3.1). In these patients cardiac output further in-creased at a rate well in excess of that of the entirecohort throughout pregnancy, even after a diagnosis ofgestational hypertension. After 36 weeks’ gestation,therefore, a high cardiac output was very stronglyassociated with gestational hypertension, with an RRratio of 123 (95% CI 12.2, 1235) and a mean value of 8.99L/minute (range 8.18–10.74, P # .001). Total peripheralresistance in this gestational hypertensive cohort was amore heterogenous variable early in pregnancy, with noapparent statistically significant association betweenresistance and outcome. These women had generallynormal total peripheral resistances during most of theirpregnancies. However, close to term, lower total pe-ripheral resistance was associated with gestational hy-pertension, with an RR ratio of 0.3 (95% CI 0.1, 0.5) anda mean measurement of 922 dynes ! sec ! cm!5 (range689–1054, P # .001). This more vasodilated state con-tinued until delivery and no increase in resistance was

Figure 2. Cardiac output and total peripheral resistance in preeclamp-sia (lines) plotted against values for the entire cohort. Symbols as inFigure 1.

Figure 1. Cardiac output and total peripheral resistance in the entirecohort. The box encompasses the 25th to the 75th percentile of the data,and an internal line shows the median. The box therefore defines thecentral 50% of the data and spanned the interquartile range, and thewhiskers show the range of the data excluding outlyers, which wereplotted separately as dots or asterisks. Values more than 1.5 times theinterquartile ranges above the 75th or below the 25th percentile areplotted as dots, and observations more than three interquartile rangesdistant are plotted as asterisks.

VOL. 94, NO. 6, DECEMBER 1999 Bosio et al Hemodynamics in Preeclampsia 981

was therefore reversed, with an RR ratio of 0.2 (95% CI0.1, 0.5).

Normal total peripheral resistance was associatedwith subsequent preeclampsia at 10–14 weeks, with anRR ratio of 0.8 (95% CI 0.6, 1.1) and mean value of 1082dynes ! sec ! cm!5 (P " .114). A normal peripheralresistance thereafter was maintained throughout thepreclinical course of pregnancy in these patients (Table2). A marked increase in total peripheral resistance wasobserved subsequently in these patients during theclinical course of preeclampsia. Thus, after 36 weeks’gestation, when all remaining patients were diagnosedas preeclamptic, a higher peripheral resistance wassignificantly associated with the condition (RR ratio 4.6,95% CI 2.3, 9.4), with a mean measurement of 1687dynes ! sec ! cm!5 (range 1383–2451, P # .001).

Figure 3 shows the measurements of cardiac outputand total peripheral resistance in individual womenwho had gestational hypertension plotted against the

entire cohort. High cardiac output was significantlyassociated with subsequent gestational hypertension asearly as 10–14 weeks’ gestation (RR ratio 1.9, 95% CI1.2, 3.1). In these patients cardiac output further in-creased at a rate well in excess of that of the entirecohort throughout pregnancy, even after a diagnosis ofgestational hypertension. After 36 weeks’ gestation,therefore, a high cardiac output was very stronglyassociated with gestational hypertension, with an RRratio of 123 (95% CI 12.2, 1235) and a mean value of 8.99L/minute (range 8.18–10.74, P # .001). Total peripheralresistance in this gestational hypertensive cohort was amore heterogenous variable early in pregnancy, with noapparent statistically significant association betweenresistance and outcome. These women had generallynormal total peripheral resistances during most of theirpregnancies. However, close to term, lower total pe-ripheral resistance was associated with gestational hy-pertension, with an RR ratio of 0.3 (95% CI 0.1, 0.5) anda mean measurement of 922 dynes ! sec ! cm!5 (range689–1054, P # .001). This more vasodilated state con-tinued until delivery and no increase in resistance was

Figure 2. Cardiac output and total peripheral resistance in preeclamp-sia (lines) plotted against values for the entire cohort. Symbols as inFigure 1.

Figure 1. Cardiac output and total peripheral resistance in the entirecohort. The box encompasses the 25th to the 75th percentile of the data,and an internal line shows the median. The box therefore defines thecentral 50% of the data and spanned the interquartile range, and thewhiskers show the range of the data excluding outlyers, which wereplotted separately as dots or asterisks. Values more than 1.5 times theinterquartile ranges above the 75th or below the 25th percentile areplotted as dots, and observations more than three interquartile rangesdistant are plotted as asterisks.

VOL. 94, NO. 6, DECEMBER 1999 Bosio et al Hemodynamics in Preeclampsia 981

Maternal Central Hemodynamics inHypertensive Disorders of Pregnancy

PAUL M. BOSIO, MD, PETER J. MCKENNA, MD, RONAN CONROY, ANDCOLM 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, fromthe traditional view that it is a vasoconstricted hypo-perfusion disorder to the view that it is a low peripheralresistance, high cardiac output state.1–4 Much of thedata are confounded by the fact that preeclampticpatients have different severity and duration of thedisease and had different clinical treatment before he-modynamic monitoring. Hemodynamic profiles atstudy 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 withcoexistent medical problems have contributed to thedisparity of findings.

By contrast, hemodynamic investigations during thelatent phase of preeclampsia are scarce. In the longitu-dinal study of Easterling et al,6 cardiac output wasconsistently higher during the latent and clinical stagesof the disease in 9 subjects in whom preeclampsiadeveloped. Visser and Wallenburg,5 on the other hand,reported that their preeclamptic patients were charac-terized by a uniform pattern of low cardiac index andhigh systemic vascular resistance before treatment.

A hypothetical disease model characterized by uni-form vasoconstriction and hypoperfusion throughoutthe latent and clinical phases of preeclampsia is notconsistent with much of the existing data. This discrep-ancy suggests that the hemodynamic features of thedisease are more complex than originally postulatedand could also change during the evolution of thepathophysiologic process. Once the condition has be-come clinically evident cross-sectional studies are un-likely to provide meaningful information about thenature of the disease in early pregnancy. Our objectivewas to clarify the evolution of this dynamic circulatorydisease by using noninvasive hemodynamic monitoringin a large prospective study commencing in earlypregnancy, before the clinical signs of preeclampsia areapparent.

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 andThe Monkstown Hospital Research Foundation.

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

Materials and MethodsThe Rotunda Hospital, Dublin, Ireland, is a large,tertiary referral maternity unit, at which 6200 deliveriestook place during the study period. A cohort of 400healthy primigravidas were recruited randomly fromthe antenatal clinics between March 1996 and March1997. Written, informed consent was obtained beforeinclusion, and approval was obtained from the Hospitalethics committee. All patients were recruited between10 and 14 weeks’ gestation.

Specific exclusion criteria at the time of recruitmentincluded a history of cardiac disease or suggestion ofchronic hypertension, chronic illness or long-term useof medication, and multiple pregnancy. In addition, allsubjects had baseline diastolic blood pressures less than90 mmHg; were considered normal on the basis ofphysical examination, electrocardiography, and echo-cardiography; and had normal hemoglobin and hemat-ocrit levels at the time of recruitment. Gestation wasconfirmed by ultrasound examination.

All subjects were monitored longitudinally through-out pregnancy by using Doppler echocardiographyperformed by a single observer (PMB) who used anATL HDi 3000 ultrasound system (ATL, Seattle, WA)with a dedicated cardiology computation package. As-cending aortic velocities were recorded from the su-prasternal notch, using an independent continuous-wave Doppler transducer, and the aortic flow velocityintegral was determined by integration of the areaunder each Doppler flow curve. Aortic annular diame-ter was measured from the left parasternal long axiswindow using two-dimensional phased-array echocar-diography. This methodology has been reviewed exten-sively and validated in pregnancy by Robson et al.7

Cardiac output (CO) was thus calculated at each mon-itoring session according to the formula:

CO !L ! min"1# ! cross-sectional area !cm2#

" velocity integral !cm# " heart rate !min"1#.

Subjects were studied in a warm, quiet environment.All measurements were made with the subject in asemirecumbent, left-lateral position after at least 10minutes’ rest. Blood pressure was measured using amercury sphygmomanometer according to recommen-dations of the American National High Blood PressureEducation Working Group.8 Heart rate was recordedfrom a simultaneous three-lead electrocardiogram.Echocardiography was performed when patients werehemodynamically stable, ie, when three consecutivereadings of blood pressure (BP) and heart rate werewithin 5%. Measurements for blood pressure and heartrate were recorded before, during, and after echocardi-ography and mean values calculated.

Total peripheral resistance (TPR) was calculated ac-cording to the formula:

TPR !mean arterial pressure !mmHg#

cardiac output !L ! min"1#

" 80 dynes ! sec ! cm"5

where mean arterial pressure

!2 " diastolic BP # systolic BP

3 .

We did a reproducibility study before recruitmentusing 20 pregnant women at different gestations. Ineach subject, cross-sectional echocardiographs andDoppler waveforms were numbered and recorded onvideotape by the same observer, on two occasions30–60 minutes apart. These were subsequently maskedand analyzed in random order 2 weeks later. Intraob-server variability was calculated as 2.4% for cardiacoutput and 3.0% for total peripheral resistance. Tempo-ral variability was calculated as 2.9% for cardiac outputand 3.4% for total peripheral resistance.

The primary outcome measures selected were thedevelopment of preeclampsia and gestational hyperten-sion as defined by Davey and MacGillivray9 and ap-proved by the International Society for the Study ofHypertension in Pregnancy. Hypertension was there-fore defined as a single diastolic blood pressure readingof at least 110 mmHg or two consecutive diastolic bloodpressure readings of at least 90 mmHg more than 4hours apart. Significant proteinuria was defined as24-hour total urinary protein excretion of 300 mg ormore. The presence of hypertension and significantproteinuria was required for a diagnosis of preeclamp-sia. Patients who met the criteria for hypertensionalone, in the absence of significant proteinuria at anytime, were diagnosed as having gestational hyperten-sion. The investigator was masked to previous hemo-dynamic measurements and to the presence or absenceof proteinuria at each monitoring session.

Patients who had significant obstetric or medicalcomplications during pregnancy, other than hyperten-sive disease, were excluded from analysis. All patientsdiagnosed as hypertensive had hemodynamic monitor-ing before therapeutic intervention. Five hemodynamicmonitoring episodes were done in each subject, the firstat 10–14 weeks, and then at 20–24 weeks, 28–32 weeks,34–36 weeks, and 37–40 weeks’ gestation, unless earlierdelivery had taken place.

Data were analyzed using Data Desk Version 6 (DataDescription Inc., Ithaca, NY) and Stata Version 5 (StataCorporation, College Station, TX). Box and whiskerplots were used to examine the temporal course of thehemodynamic factors studied. Multinomial logistic re-

VOL. 94, NO. 6, DECEMBER 1999 Bosio et al Hemodynamics in Preeclampsia 979

Maternal Central Hemodynamics inHypertensive Disorders of Pregnancy

PAUL M. BOSIO, MD, PETER J. MCKENNA, MD, RONAN CONROY, ANDCOLM 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, fromthe traditional view that it is a vasoconstricted hypo-perfusion disorder to the view that it is a low peripheralresistance, high cardiac output state.1–4 Much of thedata are confounded by the fact that preeclampticpatients have different severity and duration of thedisease and had different clinical treatment before he-modynamic monitoring. Hemodynamic profiles atstudy 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 withcoexistent medical problems have contributed to thedisparity of findings.

By contrast, hemodynamic investigations during thelatent phase of preeclampsia are scarce. In the longitu-dinal study of Easterling et al,6 cardiac output wasconsistently higher during the latent and clinical stagesof the disease in 9 subjects in whom preeclampsiadeveloped. Visser and Wallenburg,5 on the other hand,reported that their preeclamptic patients were charac-terized by a uniform pattern of low cardiac index andhigh systemic vascular resistance before treatment.

A hypothetical disease model characterized by uni-form vasoconstriction and hypoperfusion throughoutthe latent and clinical phases of preeclampsia is notconsistent with much of the existing data. This discrep-ancy suggests that the hemodynamic features of thedisease are more complex than originally postulatedand could also change during the evolution of thepathophysiologic process. Once the condition has be-come clinically evident cross-sectional studies are un-likely to provide meaningful information about thenature of the disease in early pregnancy. Our objectivewas to clarify the evolution of this dynamic circulatorydisease by using noninvasive hemodynamic monitoringin a large prospective study commencing in earlypregnancy, before the clinical signs of preeclampsia areapparent.

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 andThe Monkstown Hospital Research Foundation.

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

Figure 4 shows CO plotted against MBP for each patientwith isometric lines of TVR.

Table 4 shows the main diastolic features of the 3 groupsat 24 weeks gestation and at 1 year postpartum follow-up.During pregnancy (Table 4) late PE was characterized by thelongest DtE and the lowest E/A ratio, compared to early PEand controls. IVRT, E wave, and A wave were similar whencomparing late PE and controls, whereas early PE showed theshortest DtE, the longest IVRT with the lowest values of theA wave parameters when compared with both controls and

late PE. In the postpartum (Table 4) early and late PE patientsshowed lower E wave, and E/A ratio compared to controls.DtE was longer in late versus Early PE and controls andIVRT showed the longest value in early PE.

Intragroup comparisons in controls showed significantly(P!0.05) higher E wave velocity, shorter DtE, lower Awave velocity, time-velocity integral, and duration, longerIVRT, and higher E/A ratio in the postpartum compared topregnancy.

Intragroup comparisons in the early PE showed a signifi-cantly (P!0.05) longer DtE, lower E wave velocity, higher Awave velocity, and lower E/A ratio in the postpartum com-pares to pregnancy.

Intragroup comparisons in the Late PE showed a signifi-cantly (P!0.05) shorter DtE, lower A wave time-velocityintegral, and duration, and longer IVRT in the postpartumcompared to pregnancy.

Inter- and Intraobserver VariabilityIntra- and interobserver variability in terms of coefficient ofvariation (CV) and regression coefficient are reported. For theinterventricular septum thickness, the CVs were 7.2%(r"0.98) and 7.4% (r"0.97) for intra- and interobserver errorrespectively. For the posterior wall thickness (PWT) theywere 8.0% (r"0.98) and 8.1% (r"0.96), for the left ventric-ular diastolic diameter they were 5.0% (r"0.98) and 7.6%(r"0.97), for the left ventricular systolic diameter they were7.1% (r"0.98) and 7.6% (r"0.96), for the LVM they were8.4% (r"0.95) and 8.8% (r"0.94).

DiscussionEarly (before 34 weeks) and late (!34 weeks) onset PEprobably recognize different etiologies and therefore develop

Table 4. Parameters of Diastolic Function at 24 WeeksGestation and 1 Year Postpartum

ParameterControlsn"1119

Early PEn"75

Late PEn"32

24 weeks gestation

E wave velocity, cm/s 86#11 102#17* 86#12†

E wave time-velocity integral, cm 15#6 16#7 14#4

DtE, ms 274#40 190#62* 292#21*†

A wave velocity, cm/s 75#8 63#9* 79#5†

A wave time-velocity integral, cm 9#2 7#2* 10#3

A wave duration, ms 147#11 131#17* 149#9†

IVRT, ms 76#9 93#8* 79#5†

E/A ratio 1.17#0.23 1.68#0.50* 1.09#0.15*†

1 year postpartum

E wave velocity, cm/s 95#15 89#17* 86#18*

E wave time-velocity integral, cm 15#5 16#7 14#5

DtE, ms 211#57 224#58* 252#58*†

A wave velocity, cm/s 65#9 72#12* 73#15*

A wave time-velocity integral, cm 7#1 7#2 8#2

A wave duration, ms 129#17 134#17 139#14

IVRT, ms 84#9 94#11* 84#6†

E/A ratio 1.53#0.47 1.26#0.26* 1.21#0.27*

*P!0.05 vs controls.†P!0.05 vs early PE.

BMI

0 20 40 60 80 100

100

80

60

40

20

0

100-Specificity

Sens

itivity Sensitivity: 59.4

Specificity: 82.3 Criterion : >25.8

Figure 3. This ROC curve reports the cut-off value of prepreg-nancy BMI for the prediction of late PE ($25.8 kg/m2). Sensitiv-ity, specificity, positive, and negative predictive values were59.4%, 82.5%, 8.3%, and 98.7%, respectively.

405060708090

100110120130140150

2.00 4.00 6.00 8.00 10.00 12.00 14.00CO, L/min

MBP

, mm

Hg

Early PE Late PE Control

1600 1360 1200

800

400

770

TVR, dyne s cm. . -5

Figure 4. Scatter plot of MBP vs CO detected for each subject at24 weeks in the asymptomatic phase. Isometric lines of TVR werebuilt so that it is evident the distribution of each group within thelines of TVR. Controls (open triangles) are mostly concentratedbetween the isometric lines 770 and 1360 dyn ! s ! cm%5. Patientswith subsequent early PE (closed squares) are grouped in an areaabove the isometric line of 1360 dyn ! s ! cm%5, whereas patientswith subsequent late PE (closed rhombi) are distributed under theisometric line of 770 dyn ! s ! cm%5.

Valensise et al Hemodynamics in Early and Late PE 877

by guest on November 6, 2011http://hyper.ahajournals.org/Downloaded from

Early and Late Preeclampsia : Two Different Maternal Hemodynamic States in the Latent Phase of the Disease Herbert Valensise, Barbara Vasapollo, Giulia Gagliardi and Gian Paolo Novelli Hypertension 2008, 52:873-880

OBSTETRICS

Comparison between pulse waveform analysis andthermodilution cardiac output determination in patientswith severe pre-eclampsiaR. A. Dyer 1*, J. L. Piercy1,2, A. R. Reed1, G. W. Strathie2, C. J. Lombard4, J. A. Anthony3 and M. F. James1

1 D23 Department of Anaesthesia, 2 Department of Critical Care and 3 Department of Obstetrics and Gynaecology, University of Cape Townand Groote Schuur Hospital, Observatory, 7925 Cape Town, South Africa4 Biostatistics Unit, Medical Research Council, Cape Town, South Africa

* Corresponding author. E-mail: robert.dyer@uct.ac.za

Key points† Cardiac output (CO) monitoring

may be of value in patientswith complicated severe pre-eclampsia.

† In view of potential risks ofpulmonary artery catheter(PAC) insertion, thermodilutionCO measurements werecompared with values obtainedfrom the minimally invasiveLiDCOplus monitor.

† The comparison showed astatistically but not clinicallysignificant bias after centralvenous calibration with lithium,and no significant bias afterperipheral venous calibration.

† These findings support the useof LiDCOplus forhaemodynamic monitoring inpatients with complicatedsevere pre-eclampsia.

Background. This study compared cardiac output (CO) measurements derived from pulsewaveform analysis with values obtained by thermodilution (TD), in patients with post-partum complications of severe pre-eclampsia.

Methods. Eighteen patients were recruited, 24–96 h post-delivery. After central venouscalibration of the pulse waveform analysis monitor (LiDCOplus), CO readings werecompared with those obtained by the TD method and repeated twice at 15 min intervals.The comparison was repeated after peripheral venous calibration. Further comparisonswere made in eight patients at 120 and 240 min after peripheral venous calibration.

Results. Data were pooled for measurements at 0, 15, and 30 min after calibration. For thecomparison between TD and LiDCOplus using central venous calibration, TD exhibited asignificant positive bias of 0.58 litre min21 [95% confidence interval (CI): 0.77 to 0.39]. Afterperipheral venous calibration, there was no significant bias [0.16 litre min21 (95% CI: 20.37to 0.06)]. The estimated limits of agreement for central and peripheral venous calibrationswere 22.12 to 0.96 and 21.50 to 1.20 litre min21, respectively. When comparing LiDCOplusand TD, there was no time-based effect at 120 or 240 min post-peripheral calibration.

Conclusions. Central and peripheral venous calibrations of the LiDCOplus monitor wereassociated with clinically insignificant bias when compared with TD. Limits of agreementwere within the recommendation of 30% for acceptance of a new CO technique whencompared with current reference methods. This form of minimally invasive CO monitoringmay have a valuable role in obstetric critical care.

Keywords: cardiac output; monitoring; pre-eclampsia

Accepted for publication: 26 July 2010

The LiDCOplus system (LiDCO, Cambridge, UK) has been vali-dated in a variety of clinical scenarios; however, there are novalidation studies in the peripartum period. Indications forinvasive monitoring in severe pre-eclampsia include pulmon-ary oedema, persistent oliguria, and hypovolaemic shock.1 2

In such patients, the pulmonary artery catheter (PAC) pro-vides valuable haemodynamic data, that is, pulmonary capil-lary wedge pressure, cardiac output (CO), systemic vascularresistance, and mixed venous oxygen saturation. Knowledgeof these variables helps to guide management decisions onfluid, diuretic, and vasodilator therapy, which may influencemorbidity and mortality. The insertion of the PAC ishowever an invasive procedure, with well-described compli-cations, particularly in patients with thrombocytopaenia.3

The use of a less invasive monitor of CO would be preferablein such high-risk cases. Therefore, a prospective validationstudy was undertaken in patients who had had a PACplaced for the management of complications of severe pre-eclampsia in the immediate post-partum period.

MethodsAfter approval from the University of Cape Town Ethics Com-mittee, informed written consent was obtained for the useof the LiDCOplus monitor in 18 patients in whom a PAC(Edwards Life Sciences, Irvine, CA, USA) had been introducedvia the right internal jugular vein, to assist in the medicalmanagement of complicated severe pre-eclampsia. Arterial

British Journal of Anaesthesia 106 (1): 77–81 (2011)Advance Access publication 18 November 2010 . doi:10.1093/bja/aeq292

& The Author [2010]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.For Permissions, please email: journals.permissions@oup.com

by chris elton on Novem

ber 9, 2011http://bja.oxfordjournals.org/

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nloaded from

2.5

21.

51

0.5

0–0

.5–1

–1.5

–2–2

.5

CO

diff

eren

ce (

LiD

CO

–TD

) (li

tre

min

–1)

4 6

Mean CO: LiDCO, TD (litre min–1)

Central calibration: limits of agreement and bias

8 10

–2.12

0.96

Fig 1 Bland and Altman comparison between TD and LiDCOplus after central venous calibration. Bias: 20.58 litre min21, 95% confidence inter-val: 20.77 to 20.39 litre min21. Dotted lines show limits of agreement.

21.

51

0.5

0–0

.5–1

–1.5

–2

CO

diff

eren

ce (

LiD

CO

–TD

) (li

tre

min

–1)

4 6

Mean CO: LiDCO, TD (litre min–1)

Peripheral calibration: limits of agreement and bias

8 10 12

–1.50

1.20

Fig 2 Bland and Altman comparison between TD and LiDCOplus after peripheral venous calibration. Bias: 20.16 litre min21, 95% confidenceinterval: 20.37 to 0.06 litre min21. Dotted lines show limits of agreement.

BJA Dyer et al.

80

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Thursday (cont.)

2:30 p.m. - 3:15 p.m. Coffee Break with Exhibitors and Poster Viewing

3:15 p.m. - 4:30 p.m. Poster Review #1 Moderator: Katie Arendt, M.D.

4:30 p.m. - 6:30 p.m. SOAP Business Meeting and Elections

Friday May 14, 2010 6:30 a.m. - 5:00 p.m. Registration

6:30 a.m. - 7:30 a.m. Breakfast with the Exhibitors and Poster Viewing

7:30 a.m. - 9:00 a.m. Oral Presentations Session #1 Moderator: Barbara M. Scavone, M.D.

9:00 a.m. -10:00 a.m. Gertie Marx/FAER Education Lecture: Perioperative Technology: Use and Limitations of Non and Minimally Invasive Hemodynamic Monitoring Michael R. Pinsky, M.D.

10:00 a.m. - 10:45 a.m. Coffee Break with Exhibitors and Poster Viewing

10:45 a.m. - 11:45 a.m. What’s New In Obstetrics? George R. Saade, M.D.

11:45 a.m. - 12:45 p.m. Buffet Lunch with Exhibitors and Poster Viewing

12:45 p.m. - 1:45 p.m. Clinical Update 2010 Moderator: Joanne Douglas, M.D. Serious Complication Repository Robert D’Angelo, M.D. Phenylephrine Infusions During Cesarean Section Richard M. Smiley, M.D., Ph.D. Epidural Blood Patch Michael J. Paech, MBBS, FANZCA

1:45 p.m. - 2:45 p.m. Oral Presentations #2 Moderator: Michael Froelich, M.D.

2:45 p.m. - 3:30 p.m. Coffee Break with the Exhibitors and Poster Viewing

3:30 p.m. - 4:45 p.m. Poster Review #2 Moderator: Wendy Teoh, MBBS, FANZCA

5:00 p.m. - 6:00 p.m. Fellow Welcome Reception

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8:00 p.m. - 8:45 p.m. Optional Outing ($15 fee) - San Antonio River Tour See tour information on registration form

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6:30 a.m. - 12:30 p.m. Registration

7:30 a.m. - 9:00 a.m. Best Paper Presentations Moderator: Holly Muir, M.D. Judges: Michael J. Paech, MBBS, FANZCA; Stephen H. Halpern, M.D.; Barbara Leighton, M.D.; Lawrence C. Tsen, M.D.; James C. Eisenach, M.D.

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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

Shibli and Russell IJOA 2000 9 3 160-167

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 creatinine. •  Regularly check reflexes. Levels controversial

Conclusion

•  Maternal Mortality of PET is still high in many parts of the world

•  Obtund the pressor response to intabation •  Spinal Anaesthesia is a reasonable choice

for CS-but prepare to be surprised •  Syntocinon may cause significant

problems in preeclampsia

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), 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

•  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

•  HELLP Syndrome •  Incidence estimates vary from 0.5 to 7.6 per 1000 •  Between 8% and 24% of cases with severe preeclampsia •  more likely to be older, of white ethnicity and multiparous,

UK Obstetric Surveillance System

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) •  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