Asian Intensive Care: problems & solutions
International Intensive Care conference, Hong Kong, November 28th-30th 2007
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Marcelle Michail, MBBS, FRCA

The current recommended classification is that by the International Society for the Study of Hypertension (ISSHP). This recognised four categories in pregnancy.

Gestational hypertension and/ or proteinuria developing during pregnancy after 20 weeks’ gestation in a previously normotensive, non-proteinuric woman.

• Hypertension without proteinuria
• Proteinuria without hypertension
• Gestational proteinuric hypertension (pre-eclampsia)

Chronic hypertension and chronic renal disease

• Chronic hypertension without proteinuria
• Chronic renal disease diagnosed before, during or persisting after pregnancy
• Chronic hypertension with superimposed pre-eclampsia

Unclassified hypertension and/ or proteinuria, which is found at the first antenatal, visit after 20 weeks’ gestation in a woman whose past hypertensive status is unknown.

Eclampsia is the occurrence of generalised convulsions during pregnancy, labour or within 7 days of delivery in the absence of epilepsy or another condition predisposing to convulsions.

The ISSH defines hypertension in pregnancy as:

1. One reading of diastolic pressure exceeding 110 mm Hg or
2. Two consecutive diastolic arterial pressures of 90 mm Hg or greater at an interval of at least 4 h.

Recently it has been proposed that a rise of more than 15 mm Hg above value obtained at < 20 weeks gestation or absolute value 140/90 mm Hg may identify a group of women with pre-eclampsia more accurately.

Diastolic pressure should be recorded using Koratkoff IV sounds.

Pre-eclampsia complicates 3-5% of first pregnancies with 5-10% 0f cases being severe. It accounts for 16% of maternal deaths in the UK.

Severe pre-eclampsia exists if one or more of the following is present:

• Arterial pressure > 160 mm Hg systolic or > 110 mm Hg diastolic on two occasions at least 6 h apart
• Proteinuria > 5 g in 24 h or > 3 + on dipstick
• Oliguria < 400 ml/day
• Cerebral signs: headache, blurred vision or altered consciousness
• Pulmonary oedema or cyanosis
• Epigastric or right upper quadrant pain
• Impaired liver function
• Hepatic rupture
• Thrombocytopenia
• HELLP syndrome

Note that no feature of pre-eclampsia is consistently present and although they can be used to recognise pre-eclampsia their absence never excludes it. Pre-eclampsia becomes eclampsia with any degree of hypertension if convulsios occur.

• Generally accepted that the essential disorder is utero-placental ischaemia.
• It has been proposed that abnormal placental function, perhaps related to immune mechanisms lead to altered placental prostacyclin/thromboxane ratio, platelet aggregation, thrombin activation and fibrin deposition in maternal systemic vascular beds.
• Another proposal is that poor placental perfusion is due to abnormal placentation: endovascular trophoblast invasion remains superficial, rarely if ever reaching the myometral segments. As a result the maternal spiral arteries remain muscular and undilated with consequent placental hypoperfusion.

CNS

• Previously thought that the convulsions occur as a result of cerebral oedema. However, recent work suggests that the underlying pathology is vasospastic ischaemic injury.
• Where convulsions are severe and prolonged cerebral oedema can occur but this is probably a consequence rather than a cause.

CVS

• A review of the literature concludes that, compared to normal pregnancies, intravascular volume is reduced, cardiac output decreased and SVR increased.
• Increased sensitivity to normal circulating pressor agents including vasopressin, noradrenaline and angiotensin II. Sensitivity to latter antedates clinical presentation by weeks to months.
• In severe pre-eclampsia, plasma albumin decreased due to across leaky capillaries.

Coagulation

• Maternal vascular prostcyclin is reduced and platelet thromboxane A₂ production is increased. The resulting imbalance contributes to platelet activation and vascular damage.
• Activation of clotting cascade is consistent finding although often not clinically apparent. In some cases changes may antedate clinical evidence of pre-eclampsia by several weeks.
• Thrombocytopenia occurs in 1/3 of pre-eclamptic women and DIC in 7%.

Respiratory system

• Pulmonary oedema is not uncommon
• Occurs in about 3% of patients with severe pre-eclampsia and eclampsia; 70% of the cases develops pulmonary oedema about 70 hours after delivery. It occurs more commonly in association with multiple organ dysfunction than as an isolated complication.
• Occurs as a result of (a) a low COP in association with increased intravascular hydrostatic pressure, and (b) increased capillary permeability.
• PVR normal or reduced
• Laryngeal oedema

Liver

• The cause of the hepatic dysfunction is not clear but it may result from periportal hepatic necrosis, subcapsular haemorrhage or fibrin deposition in hepatic sinusoids.
• Spontaneous hepatic rupture is rare but potentially lethal complication, which carries 60% mortality.
• The impaired liver function can affect clearance of drugs metabolised by the liver.

Renal

• The type of proteinuria in pre-eclampsia is non-selective; the increased permeability allows large molecular weight proteins to appear in the urine.
• The majority of cases have mild to moderately diminished renal perfusion and glomerular filtration. This is caused by glomerular swelling, narrowing of the glomerular capillary lumen and fibrin deposition in the endothelial cells (glomerular capillary endotheliosis).
• Acute tubular necrosis is often the cause of the reversible renal failure and this has a good prognosis.
• Abruptio placentae, DIC and hypovolaemia usually precede the renal failure.

Feto-placental unit

• Impairment of placental perfusion caused by placental disease and vasospasm almost certainly the major reason for the high incidence of fetal loss, intrauterine growth retardation and perinatal mortality.
• It has been found that there is a shift of the oxyhaemoglobin curve to the left in these patients and this decrease oxygen availability.

• Currently, there is no ideal predictive test that fulfils all desired criteria.
• The two most important predictive factors remain nulliparity and family history.
• Uterine artery Doppler: may detect abnormal waveforms at 16-18 weeks gestation (due to impaired trophoblastic invasion of the spiral arteries)
• Elevated maternal levels of plasma urate have been shown to correlate with the risk of fetal mortality and are widely used as an indication for early delivery.

• First pregnancy
• History of chronic hypertension
• Renal disease
• Family history of pre-eclampsia
• Multiple pregnancy
• Diabetes mellitus
• Hydatidiform mole
• Hydrops fetalis

Multicentre study aimed to investigate benefits of low dose aspirin (60 mg) and any fetal/neonatal or maternal side effects

It was concluded that:

1. Routine prophylactic or therapeutic use of antiplatelet therapy for all women at risk of developing pre-eclampsia or IUGR is not recommended.
2. There is a small risk of increased peripartum haemorrhage.
3. Groups of patients who benefit history of early onset pre-eclampsia and preterm delivery.
4. No increased neonatal morbidity or mortality.
5. No increased maternal mortality.

Calcium

Recent studies demonstrated that calcium supplements reduced the incidence of hypertension, pre-eclampsia and preterm delivery. Controlled trials are needed to confirm if there is any significant reduction in perinatal mortality.

Management of pre-eclamptic ideally should be multidisciplinary.

Control of blood pressure

• It is recommended that arterial pressure of greater than 170/110 mmHg should be treated with urgency with the aim of maintaining pressure below 170/110 but above 130/90 mmHg. The aim should be to prevent intracerebral haemorrhage while not affecting uteroplacental blood flow and maternal renal function. Precipitous reduction in blood pressure should be avoided by adequate volume expansion before the use of vasodilators.
• In mild cases, blood pressure control can usually be achieved within 12 hours by oral loading and then regular dosing with methyldopa, augmented with hydralazine if necessary.

In case of severe refractory hypertension:

• Hydralazine:

• the most widely used agent
• Main advantage is the extensive experience of its use
• given either as intermittent bolus doses (5- 10 mg every 20 min
• or as continuous infusion (5- 20 mg/hr) following an initial 5 mg
• bolus
• onset of action: 20 –30 min
• one of the drawbacks of hydralazine is that its side effects (headache, tremor and vomiting) mimic the symptoms of impending eclampsia
• Labetalol

• given either as bolus dose of 50 mg repeated at 30 min as necessary or as continuous infusion at 20- 160 mg/hr
• Onset of action: 5- 20 min
• Equally effective to hydralazine, sometimes preferable because of relative freedom from maternal side effects
• Contraindications:

• asthmatic patients

• severe pre-eclampsia - impairs the capacity of the fetus to cope with intrauterine stress and it may attenuate the usual signs of fetal distress

• Nifedipine:
• unlicensed for use in pregnancy
• Shown to be satisfactory in the management of hypertension in pregnancy
• Should be used with caution if MgSO4 is being given concurrently as potentiation may occur leading to profound hypotension

• Other antihypertensives such as GTN and SNP are used less frequently as their hypotensive effect occurs rapidly with a risk of hypotension and reduced uteroplacental blood flow. Direct arterial pressure measurement is recommended

• GTN: - initial rate of infusion at 10 mg/min titrated against response. Risk of methaemoglobinaemia if a dose of 7 mcg/kg/min is exceeded

• SNP: -initial dose 0.25 mcg/kg/min, increased according to response. Risk of fetal cyanide toxicity and death (recent studies failed to show evidence of cyanide accumulation in the fetus)

• Felt to be indicated if fits thought to be imminent in some units while others start treatment only after first fit.
• Dispute regarding the most effective means of controlling convulsions with most British and European doctors using anticonvulsant and most American using MgSO₄.

Aim: to compare MgSO₄, diazepam and phenytoin in the treatment of eclampsia (multicentre study).

Conclusions:

1. MgSO₄ should be the drug of choice for eclampsia
2. Phenytoin caused more maternal and neonatal morbidity
3. Diazepam and phenytoin had more recurrent convulsions compared with MgSO₄

A large multicentre trial (MAGPIE Trial) is now underway comparing MgSO₄ with placebo in women with pre-eclampsia.

Loading dose: 4-6 g IV over 15 min

Maintenance: 1-2 g/hr infusion for at least 24 hr after the last convulsion

Toxicity:

When MgSO₄ is used monitoring should include regular measurement of plasma concentration of Mg and assessment of tendon reflexes for hypotonia.

1. Patient at term or at a gestation where viability of the fetus is not a concern
2. At any stage of pregnancy for:

• Maternal complication such as:

• Renal failure

• Hepatic disorder

• DIC or falling platelet

• Eclampsia

• Fetal complications such as:

• Chronic fetal compromise

• IUGR

• Oligohydramnios

• Doppler abnormalities

• Acute fetal compromise

• Cardiotocographic abnormalities

• Placental abruption

• The definition of oliguria used in clinical practice includes a urine output of < 20-30 ml/hr for 2 consecutive hours. The diagnosis of oliguria should be based on at least a 4 hours period.
• The most appropriate initial management is fluid management. If there is no response to a fluid challenge, CVP/PAWP should be measured before deciding further treatment. Repetitive unmonitored fluid administration should be avoided as this may lead to pulmonary oedema especially in the postpratum period.
• Poor renal function in these patients has a good prognosis.

• Regional anaesthesia has been the anaesthetic management of choice for labour and caesarean section in pre-eclamptic patients.
• Epidural analgesia reduces plasma catecholamines levels as well as improving intervillous blood flow.
• A coagulopathy is considered an absolute contraindication to regional analgesia. The risk of epidural haematoma is difficult to quantify and may occur spontaneously even in the absence of risk factors. It has been recommended that regional block should be avoided if platelet count is less than 80.000/mm³ or the bleeding time is prolonged.
• The risk of epidural haematoma with the use of low-dose aspirin has not been quantified, but in the CLASP study there has been no epidural complication that could be attributable to the use of aspirin.
• The choice of anaesthetic technique in pre-eclamptic requiring caesarean section is controversial. A well-managed incremental epidural anaesthesia is the technique of choice for most patients, providing relatively smooth control of blood pressure, maintaining utero-placental perfusion, optimising fetal outcome and eliminating the airway and haemodynamic problems associated with general anaesthesia.
• Spinal anaesthesia is often discouraged in patients with pre-eclampsia because of the risk of severe hypotension. This view has been challenged by a recent study, showing a poor correlation between the degree of hypotension during regional anaesthesia and neonatal umbilical acid-base status.
• General anaesthesia, if required, can present problems; these include:

1. Potentially difficult intubation, laryngeal oedema may not become apparent until laryngoscopy
2. Exaggerated hypertensive response to intubation may increase the risk of cerebrovascular accident, increase myocardial oxygen requirement, induce cardiac arrythmias, induce pulmonary oedema and reduce uterine blood flow. MgSO₄ has been used to control both catecholamine release and the pressor response. It was found that pre-treatment with 40 mg/kg is superior to either lignocaine or alfentanil. Short acting opioids have been used at induction of anaesthesia e.g. fentanyl 2.5 mcg/kg and alfentanil 10 mcg/kg. Esmolol proved to be useful not only for intubation but also for extubation due to its rapid onset and short duration of action.
3. Impaired intervillous blood supply.
4. Difficulties related to neuromuscular blockers in the mother receiving MgSO_4. Fasiculations may not occur after suxamethonium, with potentiation if the action of non-depolarising agents.
5. Potential aspiration of gastric content.

• Occurs in approximately 0.04% of deliveries.

• Teenage patients and mother with multiple pregnancies have a higher risk of developing fits.
• Eclampsia, which occurs antenatally, carries more complications than when the condition develops in the intrapartum or postpartum periods.
• Complications include:

1. HELLP syndrome
2. DIC
3. ARF
4. Pulmonary oedema
5. Cardiorespiratory arrest
6. Aspiration of gastic content
7. Neurological abnormalities

• Transient deficit
• Transient cortical blindness
• Retinal detachment
• Intracerebral bleed

• Haemolysis, elevated liver enzymes and low platelet count
• Severe form of pre-eclampsia. Complicates 0.3% of all pregnancies and between 4 and 20% of those with severe pre-eclampsia. 30% of the cases occur in the postpartum period. Associated with increased maternal and fetal mortality and morbidity.
• The clinical signs and symptoms include epigastric pain, upper abdominal tenderness, proteinuria, hypertension, jaundice, nausea and vomiting. The syndrome may occur in the absence of overt hypertension. The disease may progress to haematuria, oliguria, acute tubular necrosis, cortical necrosis and hypopituitarism.
• Laboratory values used to diagnose HELLP syndrome are:

1. Haemolysis, defined by abnormal peripheral blood smear
2. Increased bilirubin (³ 1.2 mg/dl) or increased lactate dehydrogenase (³ 600 u/l)
3. Increased serum aspartate aminotransferase (³ 70 u/l)
4. Low platelet count (< 100 ´ 10⁹ /l)

• The ultimate treatment is delivery of products of conception. Complete recovery usually occurs spontaneously although some further deterioration of laboratory parameters may occur for 24- 48 hours.
• The choice of anaesthetic technique depends on the condition of the patient and the fetus. Regional techniques may be contraindicated because of coagulation disturbances. The drugs used should have minimal hepatic and renal metabolism. Blood glucose should be monitored as severe hypoglycaemia has been reported in the HELLP syndrome.

• Rare complication of pre-eclampsia/eclampsia
• Initially haemorrhage intrahepatic and contained by liver capsule but may rupture into peritoneal space leading to further haemorrhage, shock and death if not adequately treated
• Pre-eclamptic patients with right upper quadrant or epigastric pain should be considered at risk for this complication. Low platelets and raised transaminases increase this risk.
• Diagnosis often made at time of Caesarian for sudden onset of fetal distress. When diagnosis suspected antepartum CT, ultrasound, peritoneal lavage and hepatic arteriography are useful in making a diagnosis
• Exploratory laparotomy and C-section recommended for all cases of subcapsular haematoma diagnosed antepartum. Indications for exploratory laparotomy during any period of observation are:
  • continued need for transfusion
  • deterioration of vital signs
  • worsening pain or peritoneal signs
  • progressive expansion of haematoma
  • suspected infected haematoma.
• Survival better in patients treated by evacuation of haematoma, packing of liver bed and drainage of operative site than in patients treated with hepatic lobectomy

• 2.3% of pre-eclamptics and 23.6% of eclamptics
• Complete or partial separation of a normally implanted placenta prior to the birth of the fetus.
• Clinical features
  • third trimester vaginal bleeding. Present in 80%, concealed in 10-20%. Latter can result in development of Couvelaire uterus, in which retroplacental haemorrhage extravasates into myometrium. This may be a source of underestimation of blood loss and may lead to uterine atony after delivery
  • Pain in 50%. Uterine tenderness and contractions in > 20%. Tenderness almost invariable in severe abruption
  • DIC in severe abruption. Almost never occurs in the absence of fetal death.
• Ultrasound useful in excluding placenta praevia - main differential diagnosis.
• May need admission to intensive care for further support. (NB consideration of the fetus is usually irrelevant, as fetal death has almost invariably occurred in severe cases.)

• Associated with increased risk of pre-eclampsia but there is no evidence that treating the hypertension decreases the risk.
• Patients with only moderate hypertension should stop treatment prior to conception because of the risks of teratogenesis.
• If patients diagnosed as having chronic hypertension during pregnancy treat only those in whom it presents an immediate hazards (eg patients with BP > 170/110) using methyldopa +/- hydralazine.
• If patient already on beta-blocker it is probably safe to continue but if she has to be started on treatment methyldopa is preferable.
• If diuretics are essential for good blood pressure control they can be continued but exacerbate decreased circulating volume if pre-eclampsia supervenes.
• Reserpine and ACE inhibitors should not be used.

© Marcelle Michail September 1999

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