Critical care management of preeclampsia and eclampsia Gunnar Dahlgren, MD, PhD Department of Anesthesia and Intensive Care Karolinska University Hospital Stockholm gunnar.dahlgren@karolinska.se

The obstetric ICU patient Intensive Care Unit Delivery room Post Anesthesia Care Unit Operating room

The cause of preeclampsia is unknown Primary placental causes Secondary maternal systemic illness Ill-defined links between the two (maternal systemic inflammatory response?)

Primary changes in the vasculature Impaired endothelial production of prostacylin, and possibly NO Release of platelet-derived factors as thromboxane and serotonin Release of endothelial procoagulant factors Vasoconstriction Low grade DIC

Pathology Placenta: Spiral arteries fail to undergo physiological dilatation and show luminal disease similar to acute atherosis in non-pregnant patients Kidney: Glomerular capillary endotheliosus. Might progress to ATN or acute cortical necrosis Placenta, kidney, brain, and liver show features consistent with chronic ischemia

Inadequate cellular oxygenation Low cardiac filling pressures (CVP, PCWP), decreased plasma volume Vasoconstriction - increased SVR Low cardiac output Tissue oxygen extraction impaired Inadequate oxygen delivery and consumption

Hypertension in pregnancy Pre-existing hypertension (3-5% of pregnancies) Pregnancy-associated hypertension (12%) (occurring de novo after the 20th week of pregnancy and settling within 6 weeks after delivery) Gestational hypertension (6-7%) Preeclampsia (5-6%) Superimposed preeclampsia (25% of women with pre-existing hypertension) Lancet 2000: 356: 1260-1265

Preeclampsia/eclampsia definitions Preeclampsia: Hypertension >140/90 with proteinuria of at least 0.3g/24h Severe preeclampsia: Preeclampsia with hypertension >160/110 or proteinuria >5g/24h or multiorgan involvement Eclampsia: Convulsions in any woman who has, or then presents with, hypertension in pregnancy of any cause

Symptoms other than hypertension and proteinuria in severe preeclampsia Oliguria (<400 ml/24h) Cerebral signs (headache, blurred vision, altered consciousness) Pulmonary edema, cyanosis Epigastric or right upper quadrant pain Impaired liver function Hepatic rupture Trombocytopenia HELLP syndrome

Fetal complications of severe preeclampsia Intrauterine growth retardation Premature delivery Abruptio placentae Fetal distress/fetal demise Associated maternal risks General/regional anesthesia DIC Hemorrhage

Maternal complications of severe preeclampsia Cardiovascular dysfunction (cardiac failure, hypertension) Renal dysfunction (oliguria, reduced GFR, elevated creatinine, acute tubular necrosis, cortical necrosis) Respiratory dysfunction (ARDS, pulmonary edema) Hepatic dysfunction (elevated liver enzymes, subcapsular hematoma, HELLP syndrome) Cerebral dysfunction (encephalopathy, ischemia, cortical blindness, retinal detachment, infarction, hemorrhage, edema, eclampsia)

”Delivery of the fetus and placenta is the definitive management of severe preeclampsia. Once severe disease has been established and is progressing, delivery of the fetus and placenta must be accomplished to limit maternal risk.” Int Care Med 1997: 23: 248-255

Invasive hemodynamic monitoring There are no data from randomized controlled clinical studies illustrating the usefulness of PA-catheters or echocardiographic techniques in patients with preeclampsia Echocardiography shows good agreement with PA-catheter measurements of cardiac output CVP may be misleading and needs cautious interpretation, particularly in patients treated with vasoactive agents or plasma volume augmentation Invasive monitoring could still be considered in patients with persistant oliguria, pulmonary edema and significant blood loss in order to guide therapy Best Pract Res Clin Obst Gyn 2001: 15: 605-622

Maternal complications of severe preeclampsia Cardiovascular dysfunction (cardiac failure, hypertension) Renal dysfunction (oliguria, reduced GFR, elevated creatinine, acute tubular necrosis, cortical necrosis) Respiratory dysfunction (ARDS, pulmonary edema) Hepatic dysfunction (elevated liver enzymes, subcapsular hematoma, HELLP syndrome) Cerebral dysfunction (encephalopathy, ischemia, cortical blindness, retinal detachment, infarction, hemorrhage, eclampsia)

Cardiac failure? Untreated preeclamptic women almost always have low filling pressures and a hyperdynamic circulation

Untreated pre-eclampsia Best Pract Res Clin Obst Gyn 2001: 15: 605-622

Cardiac failure? Untreated preeclamptic women almost always have low filling pressures and a hyperdynamic circulation The situation in treated preeclamptic patients is more variable and unpredictable

Treated pre-eclampsia Best Pract Res Clin Obst Gyn 2001: 15: 605-622

Cardiac failure? Untreated preeclamptic women almost always have low filling pressures and a hyperdynamic circulation The situation in treated preeclamptic patients is more variable and unpredictable In patients with pulmonary edema a significant part of the women has a depressed cardiac performance

Pulmonary edema Best Pract Res Clin Obst Gyn 2001: 15: 605-622

Cardiac failure? Untreated preeclamptic women almost always have low filling pressures and a hyperdynamic circulation The situation in treated preeclamptic patients is more variable and unpredictable In patients with pulmonary edema a significant part of the women has a depressed cardiac performance Diastolic dysfunction, estimated with echocardiography, is not uncommon in preeclamptic patients with pulmonary edema There is an association between preeclampsia and peripartem cardiomyopathy

Hypertension Untreated severe hypertension increases the risk for cerebral hemorrhage, renal/liver dysfunction, pulmonary congestion, decreased placental perfusion, placental detachment Treatment indicated in severe hypertension Hydralazine less effective than nifedipine and equally effective as labetalol for reducing blood pressure* Side-effects (eg maternal hypotension, placental abruption, cesarean section) more frequent with hydralazine than with labetalol and nifedipine* * BMJ 2003: 327: 955-964

Oliguria Decreased plasma volume Decreased renal perfusion and glomerular filtration Pre-renal oliguria may develop to acute tubular necrosis, most often with a good prognosis Acute cortical necrosis is rare; poor prognosis Diuresis <100 ml/4h Plasma volume expansion if CVP is <5 mmHg Furosemide if fluid balance is positive Echocardiography PA catheter to optimize left ventricular preload (PCWP 12-14 mmHg) and reduce afterload appropriately

Pulmonary edema Incidence 6% in severe preeclampsia Reduced COP (from 22 in normotensive patients at term to 15 mmHg in severe preeclampsia), a further reduction in COP after delivery. A COP-PCWP difference of 4 mmHg or less is associated with pulmonary edema in critically ill non-pregnant patients (Chest 1977: 72: 709) Increased capillary permeability Possible left ventricular dysfunction (systolic and/or diastolic) Increased risk during the first day(s) post partem

HELLP syndrome Microangiopathic hemolytic anemia, consumptive thrombocytopenia, liver dysfunction 4-12% of patients with severe preeclampsia, 30% occur postpartum DIC often secondary to placental abruption, sepsis or fetal death Platelet count indirectly proportional to severity of disease Differential diagnoses: TTP, HUS, SLE, sepsis, acute fatty liver of pregnancy Complications: ARF, ARDS, hemorrhage, placental abruption, rarely liver hematoma with rupture

Lancet 1995: 345: 1455-1463

Lancet 2002: 359: 1877-1890

Eclampsia The treatment of choice for eclampsia and prophylaxis against recurrent convulsions is magnesium sulphate (Lancet 1995: 345: 1456-1463) Magnesium sulphate is also the drug of choice for seizure prophylaxis in patients with preeclampsia (Lancet 2002: 359: 1877-1890) Prophylaxis in patients with preeclampsia is however in many departments limited to patients with severe preeclampsia or impending eclampsia Stabilize maternal condition before vaginal or cesarean delivery!

Impending eclampsia Severe preeclampsia with signs of cerebral affection like visual disturbancies, headache, increased reflexes, and clonus BJA 1996: 76: 133-148

Summary Preeclampsia is a syndrome of unknown etiology with multiorgan involvement It presents with a wide spectrum of symptoms It is sometimes difficult to distinguish from other systemic diseases Severe cases may progress to MOF and death Delivery of the child and placenta is the only specific treatment – other lines of teatment are only supportive There are several issues regarding diagnostic techniques and treatment options that need further evaluation