Aims of Obstetric Critical Care Management

Best Practice & Research Clinical Obstetrics and GynaecologyVol. 22, No. 5, pp. 775–799, 2008

doi:10.1016/j.bpobgyn.2008.06.001
available online at http://www.sciencedirect.com
2

Aims of obstetric critical care management

Laura Claire Price* BSc, MBChB, MRCA, MRCP

SpR Respiratory and Intensive Care Medicine

Adult ICU, St George’s Hospital, London, UK

Andrew Slack MBBS, MRCP

SpR Renal and Intensive Care Medicine

Adult ICU, Kings College Hospital, London, UK

Catherine Nelson-Piercy MA, FRCP, FRCOG

Consultant Obstetric Physician

Directorate Office, North Wing, St Thomas’ Hospital, London, UK

The aims of critical care management are broad. Critical illness in pregnancy is especially perti-nent as the patient is usually young and previously fit, and management decisions must alsoconsider the fetus. Assessment must consider the normal physiological changes of pregnancy,which may complicate diagnosis of disease and scoring levels of severity. Pregnant womenmay present with any medical or surgical problem, as well as specific pathologies unique to preg-nancy that may be life threatening, including pre-eclampsia and hypertension, thromboembolicdisease and massive obstetric haemorrhage. There are also increasing numbers of pregnanciesin those with high-risk medical conditions such as cardiac disease. As numbers are small andclinical trials in pregnancy are not practical, management in most cases relies on general inten-sive care principles extrapolated from the non-pregnant population. This chapter will outline theaims of management in an organ-system-based approach, focusing on important general princi-ples of critical care management with considerations for the pregnant and puerperal patient.

Key words: pregnancy; high risk; complications; pre-eclampsia; postpartum haemorrhage;thromboembolism; intensive care; critical care.

GENERAL OVERVIEW

Maternal mortality is fortunately rare in the UK, with 13.95 maternal deaths per100 000 deliveries in 2003–2005.1 However, despite modern-day advances in care,

* Corresponding author. Tel.: þ44 2074311250; Fax: +44 2084584505.

E-mail address: [email protected] (L.C. Price).

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this figure has remained static over the last few decades, and this may relate to a highernumber of high-risk pregnancies progressing to term.2 Worldwide, maternal mortalityis greater with 55–920 maternal deaths per 100 000 live births3, with the highest ratesin sub-Saharan Africa. The most common reasons for intensive care unit (ICU) admis-sions in the UK are pre-eclampsia, sepsis and haemorrhage.4 Overall, 0.9% of pregnantwomen require ICU admission in the UK, comparable to US figures.5 The mostcommon cause of maternal death on ICU is acute respiratory distress syndrome(ARDS). UK maternal mortality could be improved with prompt recognition of criticalillness, earlier use of critical care facilities and earlier senior involvement. Perinatalmortality rates are up to 20–25% depending on the underlying maternal diagnosis.

The assessment and management of obstetric admissions to critical care can be chal-lenging, with unique disease states and physiological changes seen. These changes occurin all major systems and persist for up to 6 weeks post partum. In 50–80% of cases, preg-nant women require ICU admission due to a direct obstetric cause; the remainder relateto medical causes. There may be diseases specific to pregnancy (massive obstetric hae-morrhage, amniotic fluid embolism, pre-eclampsia, peripartum cardiomyopathy); an in-creased susceptibility to certain diseases due to pregnancy (venous thromboembolism,urinary tract infection, varicella pneumonia); pre-existing disease exacerbation (asthma,cardiac disease); or incidental diseases during pregnancy (e.g. diabetic ketoacidosis). Therequirement for critical care support for one or more organ failures usually results fromthe development of a multisystem disorder such as shock, ARDS or sepsis.

The aim of critical care management in any population is to ensure adequate oxygendelivery and tissue perfusion. There are specific conditions requiring attention in preg-nancy, and this review will consider general ICU principles and these with reference toobstetric physiology. The altered maternal physiology should be considered duringeach stage of assessment, resuscitation, monitoring, use of pharmacological therapies,and single or multiple organ support. Young, previously healthy patients often showrelative compensation in critical illness. The signs of sepsis and haemorrhage are oftenmasked initially and abnormal signs may overlap normal signs of pregnancy. Some signsalways indicate abnormality, including tachypnoea and metabolic acidosis. Obstetricand medical staff should be trained in the recognition of critical illness in this popula-tion as the disease processes can follow a rapid and fulminant course.

The effects on fetal perfusion are dependent on placental perfusion and oxygendelivery, both reflecting maternal wellbeing. The fetus is adapted to living in a relativelyhypoxic environment with the oxygen dissociation curve shifted to the left, highhaematocrit and high cardiac output (CO). Despite this, small changes in maternalhomeostasis may have an adverse effect on the fetus. If the mother does become crit-ically ill, premature delivery may be indicated with the associated neonatal complica-tions of respiratory distress syndrome, jaundice, intracranial haemorrhage andnecrotizing enterocolitis.

AIMS OF ORGAN SUPPORT IN CRITICAL CARE

General supportive care

Immediate resuscitation is the primary aim in the management of any critically ill pa-tient, with systematic assessment of deranged physiology using an organ-basedsystematic approach. This is generic, irrespective of the underlying pathology, and isfollowed by more specific diagnostic consideration when the patient is more stable.

Aims of obstetric critical care management 777

Appropriate investigations and procedures are then carried out, depending on theclinical history and examination. It is important not to withhold or delay useful inves-tigations because the patient is pregnant.

The gestational age and condition of the fetus must always be considered, as wellas the effects of any drugs or procedures on the fetus. The obstetric team shouldperform a fetal scan to assess viability. Often if the mother is or has been criticallyill, the fetus may have succumbed. Once this is established, liaison with obstetricsto deliver the baby will usually improve maternal physiology, although delivery itselfis associated with significant temporary haemodynamic demands and changes. If thefetus is viable, the advisability of delivery needs a multidisciplinary discussion balancingthe fetal risks of prematurity versus any maternal benefits from delivery. The moth-er’s health should be the priority. The fetus is at significant risk if the mother is se-riously ill, particularly if she is acidotic, and regular fetal monitoring is appropriate.Fetal management primarily involves maternal resuscitation, maintaining adequate pla-cental oxygenation and perfusion. Delivery may be indicated in some settings of se-vere maternal illness such as cardiac arrest, severe asthma, acute fatty liver ofpregnancy or pre-eclampsia, or with fetal distress. When considering the timing ofdelivery, the effects of drugs on fetal physiology and the requirement for neonatal re-suscitation should be considered. Drugs are classed according to the risk of fetal ef-fects into Category A (no fetal risk) to Category D (fetal risk), and Category X(contra-indicated). The maternal volume of distribution is increased and glomerularfiltration rate (GFR) is elevated in pregnancy, so higher doses are needed for drugswith renal elimination. Sedative effects on fetal respiratory function should be antic-ipated, although polarized agents such as neuromuscular blocking agents do not crossthe placenta.

Critical care involves intensive monitoring and physiological support for patientswith life-threatening but potentially reversible conditions. Patients should be managedin either an ICU (Level 3) or high-dependency (Level 2) setting. Level 3 usually involvespatients with multi-organ failure and/or requiring mechanical ventilation, while Level 2involves non-invasive ventilation (NIV), renal replacement therapy or intensivemonitoring.

Early involvement and planning should involve all members of the multidisciplinaryteam. This includes obstetricians, midwives, physicians (obstetric physicians if avail-able), intensivists, anaesthetists, haematologists, paediatricians and neonatologists.Elective ICU beds should be booked for certain patients such as those with significantcardiac disease undergoing elective caesarean section.

Early recognition of critical illness is essential. There is good evidence that earlyintervention in the first 6 h of severe sepsis influences survival. Ideally, early warningscoring systems adapted to pregnancy physiology should be implemented on obstetricwards to identify patients at an early stage. ICU care can often be commenced in theoperating theatre or emergency department (ED) prior to transfer to the ICU toavoid delays, and stabilization and elective intubation may be necessary prior totransfer.

Aims should also include adherence to recent developments in critical care prac-tice including the Surviving Sepsis Campaign guidelines6, considered use of activatedprotein C7, insulin therapy to maintain normoglycaemia8, corticosteroids in septicshock9, lung protective ventilatory strategies in ARDS management, and earlygoal-directed therapy for severe sepsis and septic shock.10 Although not writtenwith the obstetric patient in mind, most aspects of management should not differdramatically.


Haemodynamic management

The aims of cardiovascular support in any setting are to maintain adequate cardiac out-put (CO) and blood pressure (BP). There is a 20% increase in maternal oxygen de-mand in pregnancy; CO increases by 30–50% due to an increase in stroke volumeand heart rate, and BP is reduced by 5–10 mm Hg by mid-pregnancy. There is nochange in central venous pressure (CVP) or pulmonary artery wedge pressure(PAWP) as systemic and pulmonary vascular resistance are both reduced.11 These hae-modynamic changes begin as early as 8 weeks, and gradually return to normal 2–12weeks post partum.12

The supine hypotension syndrome is an important consideration after 24 weeks. Itrelates to compression of the inferior vena cava by the gravid uterus, and can lead toa dramatic drop in preload, leading to a 25–30% drop in CO, severe hypotension andbradycardia. It can be reduced by positioning in a lateral tilt although a full left lateralposition is sometimes required.

The most significant cardiovascular challenge occurs at birth. Up to 500 mL ofblood is autotransfused back into the circulation following relief of aortocavalcompression by the fetoplacental unit aortocaval compression by the fetoplacentalunit and contraction of the uterus, and CO may increase by up to 80% of pretermbaseline. These fluid shifts are especially challenging in parturients with cardiac disease,who should be monitored for 72 h post partum.13

Shock

Cardiovascular support may be required in states of circulatory shock. In shock,reduced tissue oxygenation leads to anaerobic metabolism, reflected by an increasedserum lactate and reduced maternal central venous oxygen saturations (SvO2). Thiswill affect fetal oxygenation despite adaptation to a relatively hypoxic environment.

Lactate levels >2 mmol/L indicate tissue hypoxia except in settings with poorlactate clearance such as liver failure. Serial measurements are useful, for example,in septic shock (Table 1).14

The most common causes of shock in the obstetric population are major haemor-rhage and sepsis. When reversible causes have been controlled, support of the

Table 1. Types of shock.

Type of shock Pathophysiology Cardiac

output

Systematic

vascular

resistance

Examples of causes

Hypovolaemia Loss of circulating

volume

Low High Massive haemorrhage, diabetic

ketoacidosis, burns

Distributive Pathological

vasodilatation

High/low Low Sepsis, liver failure, pancreatitis,

anaphylaxis

Cardiogenic Severe pump failure Low High Cardiomyopathy, valvular dysfunction

Obstructive Obstruction to

cardiac output

Low High Pulmonary embolism, amniotic fluid

embolus, tamponade

Neurogenic Loss of sympathetic

outflow if lesion

above T6

Low Low Spinal trauma, intracranial haemorrhage


cardiovascular system may involve fluid administration, correction of heart rate andrhythm disorders, the use of vasoactive agents, thrombolysis, pacemakers, ventilatorysupport and mechanical devices. Invasive or non-invasive haemodynamic monitoring isan important tool. Techniques may be invasive (lithium dilution pulsed contour analysisand the pulmonary artery catheter), semi-invasive (oesophageal Doppler) or non-inva-sive (echocardiography).

Fluids

Fluid administration is an important part of most resuscitation scenarios, aiming toimprove microvascular blood flow by increasing plasma volume, and improve CO bythe Frank-Starling mechanism.15 However, the use of fluids in obstetrics should bemore cautious than in the non-obstetric setting. Even in a normal pregnancy, colloidoncotic pressure (COP) is reduced by 14% (from 20.8 to 18 mm Hg).16 This reductionin COP, when combined with any condition predisposing to either increased capillaryleak (e.g. in pre-eclampsia and many critical illness states) or raised left atrial pressure,can relatively easily lead to pulmonary oedema.17 It is not thought to be as common asthis suggests, because pulmonary lymphatic drainage is increased in pregnancy.

The choice of fluid used will depend on the setting. In major haemorrhage, replace-ment is needed with blood products. Otherwise, the choice between crystalloid andcolloid remains under debate. Excessive use of normal saline leads to hyperchloraemicacidosis18, and Hartmann’s solution is currently the most ‘physiological’ crystalloid inuse. Colloids remain in the intravascular compartment for longer. Overall, the choicewill depend on the underlying diagnosis, local availability, the evaluation of the contentof each fluid type, and the benefits and complications of each (see Table 2).19

The concept of a fluid challenge requires haemodynamic monitoring to assessvolume responsiveness to a set volume of fluid.20 Following this, a 20% rise in strokevolume suggests intravascular depletion, and sufficient intravascular volume is sug-gested when the rise is sustained. Small rises or a fall in the stroke volume suggest fluidoverload as the myocardium is stretched ‘over the Starling curve’. Obstetric patientsare best managed with a neutral or even negative fluid balance, as the development ofacute prerenal failure is usually reversible if recognised and treated early, comparedwith the potential risks of non-cardiogenic pulmonary oedema or ARDS.

Table 2. Fluid composition.

Fluid Ionic content (mmol/L) pH Complications

Normal saline

(NaCl 0.9%)

Naþ 154, Cl� 154 5.0 Hyperchloraemic acidosis

5% dextrose Nil 4.0 Hyponatraemia, oedema

Hartmann’s

(compound Na lactate)

Naþ 131, Kþ 5, Cl� 111,

Ca2þ 2, HCO3- 29

6.5 Fluid overload

(with all fluids), Kþ may

accumulate

Gelofusin Naþ 154, Kþ 0.4, Cl� 154,

Ca2þ 0.4

7.4 Allergy (<0.1%),

hyperchloraemia

Albumin 4.5% Naþ 150, Kþ 2, Cl� 120 7.4 Transfusion reactions,

TRALI

TRALI, transfusion-related lung injury.


Furthermore, the appropriate management of oliguria in these patients is not neces-sarily a fluid challenge, as discussed further in the renal section.

Cardiac failure

Cardiac failure may be primarily left sided with pulmonary oedema, right sided with ev-idence of hepatic and renal congestion, or biventricular. Reversible causes such as coro-nary ischaemia or pulmonary embolism should be managed as appropriate. Non-invasivecontinuous positive airways pressure (CPAP) is a very effective treatment for cardiogenicpulmonary oedema21,22, and will increase CO, reduce left ventricular afterload, increasefunctional residual capacity (FRC) and respiratory mechanics, and reduce work ofbreathing. Invasive ventilation may be needed if the woman is severely acidotic, hypercap-nic, hypotensive or has very poor left ventricular function.23 Vasodilator therapy is im-portant, and both glyceryl trinitrate (GTN) and hydralazine are safe in pregnancy.Loop diuretics are used to reduce pulmonary congestion, although they may reduceCO and uteroplacental perfusion if hypovolaemic. If inotropes are needed, dobutamineis safe in pregnancy. Newer inotropes such as levosimendan may improve arterioventric-ular coupling24, although there are only case reports of use in pregnancy in peripartumcardiomyopathy.25 Mechanical devices to augment CO such as ventricular assist devicesand intra-aortic balloon pumps may be required.

Vasoactive agents

Heart rate and rhythm disorders are corrected in the usual way according to resusci-tation council guidelines. Most supraventricular tachycardias and ventricular ectopicsrequire no drug therapy in pregnancy, and vagal manouevres such as carotid sinusmassage should be tried first in paroxysmal supraventricular tachycardia. Atrial fibril-lation should be restored to sinus rhythm in pregnancy with electrical cardioversion,or rate controlled with digoxin or cardioselective beta-blockers. Replacement ofpotassium and magnesium may be required, then chemical or electrical cardioversionas appropriate, or use of specific anti-arrhythmic agents. Cardioselective beta-blockers, diltiazem, verapamil and adenosine are safe; however, amiodarone shouldbe avoided as it can inhibit fetal thyroid function.26

Vasopressors are often used for hypotension in the setting of obstetric regional anaes-thesia. Ephedrine may lead to maternal tachycardia due to its chronotropic effects on thecardiac beta-1 receptor and reduced fetal pH, although it is less likely to cause uteropla-cental vasoconstriction. Phenylephrine, an alpha-1 adrenergic agonist and powerful arte-riolar constrictor, causes less fetal acidosis although it may reduce maternal heart rateand therefore CO.27 If inotropes or more powerful vasopressors are required in anICU setting, the effects on uteroplacental perfusion should be considered, and CO mon-itoring is useful. The choice of agent will depend on the mean arterial pressure (MAP),CO and systematic vascular resistance (SVR), and should follow appropriate fluid resus-citation. In the setting of vasodilatory shock with low SVR and high CO (sepsis, liver fail-ure), sympathomimetic vasopressors such as norepinephrine are used. Vasopressin hasbeen used in some settings such as resistant septic shock and cardiac arrest28, but re-duced blood flow to some organs may occur29 so it should be reserved for ‘salvage’ ther-apy.30 In cardiogenic shock, increased inotropy from beta-1 agonism may be useful usingdobutamine (and epinephrine with added vasoconstrictive effects). Inodilators are usefulwhen low CO occurs with vasoconstriction (high SVR), with agents including milrinoneand the calcium-sensitizer levosimendan (Table 3).24

Table 3. Vasoactive agents.

Use if Clinical example Important side effects

Vasopressors

Less potent

Ephedrine Low SVR Spinal/epidural/general

anaesthetic-induced

vasodilatation

All have effects on

UP perfusionPhenylephrine

Metaraminol

More potent

Noradrenaline Low SVR with

shock unresponsive

to fluid challenge

Septic shock Lowers UP perfusion;

digital necrosisVasopressin

Inotropes

Inoconstrictor

Adrenaline Low CO

þ low SVR

Septic shock Lactic acidosis

Inodilators

Milrinone Low CO

þ high SVR

Cardiogenic shock Hypotension, dose prolonged

in renal failure (milrinone)Levosimendan

Variable

Dobutamine Low CO Sometimes combined

with a vasoconstrictor

in some shock settings,

or used alone in

cardiogenic shock

Variable effects on blood

pressure (dobutamine)

Tachycardia (dopexamine)

Dopexamine Low CO with poor

splanchnic

perfusion

CO, cardiac output; SVR, systematic vascular resistance; UP, uteroplacental.


Hypertension

Hypertension complicates 12% of pregnancies31 and may be classified into pre-eclampsia,gestational hypertension, chronic essential hypertension and malignant hypertensionpresenting in pregnancy. The overall management strategy of pre-eclampsia with deliv-ery as a prime goal is discussed in detail elsewhere. There is no single ideal anti-hy-pertensive regime used for acute severe hypertension in pregnancy, and most unitshave their own protocol. Intravenous hydralazine and labetalol are equally effectivebut labetalol is preferred as it has fewer side effects.32 Sodium nitroprusside is an ef-fective vasodilator, and is therefore a good choice if pulmonary oedema is present,and its short half-life is useful when titrating the dose. However, toxicity may occurwith cyanide or thiocyanate accumulation, usually in those with renal failure and iftreated for more than 24 h. GTN is useful and safe for short-term use, althoughmainly as a venodilator as it has little effectiveness in hypertensive emergenciesand so is not usually a first-line agent, and problems result with tachyphylaxis. Oralnifedipine, doxasocin and alpha-methyldopa are oral options. Angiotensin-convertingenzyme inhibitors are teratogenic33 and are therefore contra-indicated, although theymay be life-saving in some cases of malignant hypertension including scleroderma.

Respiratory management

The overall aim of respiratory management is to maintain gas exchange. This encom-passes airway management, administering oxygen therapy and ensuring adequate


ventilation (CO2 clearance). These general principles are as for the non-pregnantpopulation, with added considerations of the physiological changes, including the leftlateral tilt in positioning, and the need in later pregnancy to consider a deliveryplan. It is important to remember that oxygen delivery to the tissues and effectiveCO2 removal involves the heart and circulation as well as the lungs. Oxygen deliveryto the tissues involves a cascade of processes depending on alveolar oxygen concen-tration, oxygen transfer, haemoglobin and the oxygen dissociation curve, then diffusionfrom capillary blood into mitochondria along a concentration gradient. Defects canoccur at any of these levels.

The differential diagnosis of primary respiratory failure in pregnancy is broad, andthe changes in respiratory physiology should be remembered in assessment andmanagement. Erect partial pressure of oxygen (PaO2) increases by the end of the firsttrimester, and falls during each of the following trimesters. This is due to an increasedarteriovenous oxygen difference as oxygen consumption increases above CO with theadvancement of pregnancy. After mid-gestation, PaO2 is <13.1 kPa in supine patientsdue to airway closing capacity being above FRC, and also from aortocaval compres-sion. The reduced FRC and greater oxygen consumption make episodes of desatura-tion more rapid. Adequate fetal oxygenation requires a maternal paO2> 9.2 kPa,corresponding to a maternal arterial oxygen saturations (SaO2)> 95%34; much higherthan the saturations usually tolerated outside pregnancy.

It is important to consider the normal progressive respiratory alkalosis when con-sidering respiratory management, as ventilation requirements may change dependingon the stage of pregnancy. In severe asthma, a ‘normal’ partial pressure of CO2

(pCO2) of 4–5.5 kPa is usually a warning of impending respiratory failure. In pregnancy,this is, in fact, relative hypercapnia as the usual upper limit in pregnancy is 3.5 kPa. Theeffects of pCO2 on fetal wellbeing are not clear, although they are likely to be detri-mental with acidosis leading to reduced ability of fetal haemoglobin to bind oxygen.A diffusion gradient of approximately 1.3 kPa is needed for placental pCO2 clear-ance35, and high maternal levels may interfere with this. A maternal pCO2 target of<5.9 kPa or pH >7.30 has therefore been suggested36, avoiding hypercapnia (Table 4).

Upper airway

Airway management may be challenging in obstetric practice. There are changes in ma-ternal anatomy with increased upper airway oedema, especially in pre-eclampsia wherefluid retention enlarges the tongue and makes identification of airway landmarks more

Table 4. Causes of respiratory failure in pregnancy.

Pulmonary causes

Asthma, severe pneumonia, pleural effusion, pneumothorax, pulmonary haemorrhage, interstitial

lung disease, exacerbation of underlying respiratory disease (e.g. cystic fibrosis, chronic obstructive

pulmonary disease, bronchiectasis, pulmonary hypertension), atypical infection (including human

immunodeficiency virus), respiratory muscle myopathies (hypercapnic respiratory failure)

Acute respiratory distress syndrome (ARDS) and acute lung injury (see later)

Cardiac causes

Cardiogenic pulmonary oedema, e.g. peripartum cardiomyopathy, mitral stenosis

Iatrogenic fluid overload

Tocolytic pulmonary oedema (rare now with alternatives to beta-sympathomimetics)


difficult.37 Any neck or face oedema in a woman with pre-eclampsia should forewarnof a likely difficult intubation.38 These patients may even develop stridor and may havedifficult extubations.39 Airway oedema in pre-eclampsia can even lead to obstructivesleep apnoea.37 Sleep-disordered breathing is probably underdiagnosed in pregnancy40

and may have adverse fetal effects.41 Obesity is more common and correlates with dif-ficult intubations42, instrumental deliveries, a higher incidence of postpartum haemor-rhage43, and an even greater incidence of gastric acid aspiration during generalanaesthesia.44 The upper airway in pregnancy is prone to contact bleeding with anyairway manipulation. This mucosal swelling leads to a smaller laryngeal inlet. Any air-way intervention should involve a skilled anaesthetist with a fluent difficult/failed intu-bation drill.

Ventilation

The aims of ventilation are to oxygenate, ventilate and relieve the work of breathing. Inpregnancy, ventilation can be problematic. As in the non-pregnant patient, ventilationmay be invasive, through an endotracheal tube or tracheotomy, or non-invasive,through a tightly fitting facemask. NIV may exert CPAP or bi-level positive airway pres-sure (BiPAP). CPAP is the application of a constant positive end-expiratory pressure,called ‘positive end-expiratory pressure’ in the invasively ventilated patient. Non-inva-sive CPAP differs from BiPAP in several ways. BiPAP enables spontaneous breathingover two pressure levels, and is therefore more effective at clearing CO2, hence itsuse in hypercapnic respiratory failure. CPAP circuits can deliver a higher fractional in-spired oxygen concentration (FiO2) and can be humidified, and the FiO2 can be mea-sured accurately. With BiPAP, FiO2 is not measured accurately, oxygen is entrained inL/min, the circuit tolerates leaks, and the delivered FiO2 is dependent on the inspira-tory flow rate.

Non-invasive ventilation. The evidence for acute NIV is well established in the treatmentof hypercapnic respiratory failure in chronic obstructive pulmonary disease, where itreduces the need for intubation in mildly acidotic patients.45 There is also good evi-dence for NIV in cardiogenic pulmonary oedema and in immunocompromised states.It has physiological benefit in other causes of respiratory failure, but should be used ina controlled, monitored setting as a trial of therapy. Patients should be awake withgood respiratory drive, haemodynamically stable and without excessive respiratory se-cretions. Those with more marked acidosis (pH <7.25) should be considered for ear-lier invasive ventilation. There is less evidence for its use in other causes ofhypoxaemic respiratory failure, but it has been used in asthma, pneumonia, ARDSand others including postoperative cases.46 There is little evidence for its use in theobstetric population, although it has been used in sleep-disordered breathing duringpregnancy.40 NIV cannot therefore be currently recommended except as a closelymonitored trial of therapy in selected obstetric patients, in an ICU setting. Further-more, there is a theoretical even greater risk of gastric acid aspiration with the gastricdistention that occurs with NIV.

Invasive ventilation. Invasive ventilatory support may be necessary in primary respira-tory failure, when a trial of NIV fails, in severe acidosis, and with reduced levels of con-sciousness and respiratory drive. The overall management of a ventilated obstetricpatient is similar to the non-pregnant population. This includes adequate thrombopro-phylaxis, enteral feeding, sedation breaks and weaning techniques. Spontaneous


breathing modes are preferred to maintain respiratory muscle strength, but increasedsedation and paralysis may be needed to optimize ventilation.47 Gastric acid suppress-ion therapy should be routine, especially with the increased risk of gastric acid aspira-tion in these patients.

It is important to prevent ventilator-associated pneumonia (VAP), thought to followbacterial colonization of the upper respiratory tract. Diagnosis based on clinical crite-ria has poor specificity, and microbiological samples are used including direct bron-choalveolar lavage48, protected specimen brush49 or non-invasive endotrachealaspiration. Biomarkers such as C-reactive protein and procalcitonin50 can be useful,although they are probably less specific in the obstetric population. Methods to pre-vent VAP include nursing ventilated patients head-up, avoiding re-intubation and min-imizing changes in ventilator circuits.51

Strategies for weaning from mechanical ventilation, including the use of weaningprotocols52, are no different to the non-obstetric population. Percutaneous tracheos-tomy insertion may be indicated early in patients requiring prolonged ventilation53,bearing in mind that the upper airway in any parturient is more oedematous and proneto contact bleeding.

Acute respiratory distress syndrome

Acute lung injury and ARDS are a disease spectrum with many underlying causes. Thediagnosis is based on three factors: the presence of pulmonary oedema; evidence ofpoor oxygenation; and clinical, echo or direct evidence of normal left atrial pressureto exclude a cardiogenic cause of pulmonary oedema.54 The extent of poor oxygen-ation is based on a ‘P:F’ ratio of PaO2 to FiO2. For example, breathing air (FiO2 0.21),the normal range of PaO2 would be 13–17 kPa, giving a P:F ratio of 72 kPa. WithARDS, the FiO2 may be 0.8 and the PaO2 only 15 kPa, giving a P:F ratio of 18.7 kPa(or 142 mm Hg), hence indicating poor oxygenation. It is always important to notethe FiO2 when measuring blood gases for this reason (Table 5).

Any pathology causing inflammation-induced injury to the alveolar–capillary inter-face can lead to ARDS. There is no suggestion that it is more common in pregnancy,but it may be the end result in several ‘obstetric’ diseases. Maternal mortality may be35–60% with higher mortality post partum, and morbidity often persisting after recov-ery in survivors (Table 6).36

Ventilatory strategies in ARDS are similar to the non-pregnant patient with consid-eration of the normal progressive respiratory alkalosis and the effects of hypoxia, hy-percapnia and acidosis on the fetus. Invasive ventilation is often necessary, and isthought to contribute to a syndrome of lung injury itself. There has recently beena drive towards a ‘lung protective’ ventilation strategy to reduce the need for invasiveventilation. The components of iatrogenic ventilator-associated lung injury includethose due to excess airway pressure (barotrauma55), too high tidal volumes (volu-trauma56), airway collapse (atelectrauma9) and local inflammation (biotrauma57). The

Table 5. Definitions of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI).54

Bilateral chest X-ray infiltrates

P/F ratio< 26 kPa (ARDS) or <39 kPa (ALI)

Pulmonary artery wedge pressure <18 mm Hg (or 2.4 kPa)

Table 6. Causes of acute respiratory distress syndrome in pregnancy.

Causes specific to pregnancy

Massive haemorrhage, pre-eclampsia (especially with fluid overload), sepsis (due to chorioamnionitis,

endometritis, pyelonephritis), amniotic fluid embolism, trophoblastic embolism, gastric acid

aspiration

Other causes

Sepsis (other causes), pneumonia, transfusion-related acute lung injury, trauma, inhalational injury,

burns, near-drowning, acute pancreatitis etc.


principles of a protective ventilation strategy in ARDS are to minimize airway pres-sures and to tolerate a higher pCO2. There are, however, fetal effects of hypercapniaand acidosis, so this ‘permissive hypercapnia’ is not recommended in the obstetric pa-tient. Furthermore, the low tidal volumes desired in ARDS in a non-obstetric patientmay not be sufficient for the higher ventilatory requirements needed in pregnancy. Infact, higher tidal volumes and plateau pressures than usual may actually be necessaryfor this reason, and higher SaO2 and pO2 targets are recommended. As in any setting,positive end-expiratory pressure is useful to prevent end-expiratory lung collapse, andcan improve recruitment and oxygenation of alveolar units. These effects may be offsetby negative effects on cardiac filling with reduced systemic BP, exaggerated with intra-vascular fluid depletion.

Renal support

The incidence of acute renal failure (ARF) in pregnancy has reduced over time in bothdeveloped (1–2.8%) and developing (10–15%) countries with improvements in obstet-ric care, especially a reduction in septic abortions.58 The World Health Organizationhas estimated that one in eight pregnancy-related deaths in the developing world arethe result of unsafe abortions and about 8% of these deaths are due to ARF.59

The diagnosis of ARF is complex with over 30 definitions of ARF in the literature.The RIFLE criteria were developed to provide a uniform means of classifying ARF;these have been modified recently and the term ‘acute kidney injury’ (AKI) hasbeen introduced to encompass all causes of ARF. The classification is based on changesin serum creatinine and/or urine output over a 48-h period.60 It is easy to apply clin-ically, and importantly highlights the requirement of repeated testing of serum creat-inine and the close monitoring of urine output in any patient with suspected or at riskof ARF.

Obstructive uropathy must always be excluded, and this can be difficult in preg-nancy due to physiological hydronephrosis, therefore an early ultrasound can providean invaluable baseline reference for the future when obstructive uropathy is suspected.Progesterone-induced ureteric smooth muscle relaxation plus compression by thegravid uterus leads to ureteric and renopelviceal dilatation. There is greater hydro-nephrosis on the right side due to physiological engorgement of the right ovarianvein and dextrorotation of the uterus.

Early recognition and treatment of AKI saves nephrons and prevents further declinein glomerular filtration rate (GFR). Serum creatinine concentration is a poor marker ofGFR because it does not rise appreciably until GFR has fallen significantly. From thefirst trimester of pregnancy until term, there are significant increases in renal blood


flow (50–85%) and GFR (40–65%); consequently, there is a parallel decline in the se-rum creatinine concentration. Therefore, small changes in the serum creatinine con-centration can represent a significant deterioration in GFR. The calculation ofestimated GFR using the modification of diet in renal disease study (MDRD) equationis not recommended in pregnancy as it overestimates GFR.

Aetiology

Conventionally, the major causes of AKI are grouped into three general categories:prerenal; intrinsic renal; and obstructive causes. This holds true in pregnancy, butmost importantly includes the placenta-driven diseases including pre-eclampsia andHELLP (haemolysis–elevated liver enzymes–low platelets) syndrome (Table 7).

Urinary electrolyte measurements are rarely helpful clinically as they are unreliablein distinguishing between prerenal failure and acute tubular necrosis, and they do notaffect management. It is useful to quantify the degree and change in proteinuria, whichrequires repeated random urine samples for protein:creatinine ratio measurement.This method has been validated in hypertensive and non-hypertensive pregnantpatients and is comparable to 24-h collections.61

Management of acute kidney injury

The mainstay of treatment in ARF is aimed at minimizing damage to surviving nephronswhilst providing support until the kidney recovers. This includes the removal of tubu-lar toxins, specific treatment of glomerular diseases and restoration of the circulation.Haemodynamic monitoring using clinical and invasive methods guides volume resusci-tation and the use of vasopressors with the goal of improving perfusion pressure andurine output (>0.5–1 mL/kg/h). Failure to achieve this goal will usually become appar-ent at an early stage, and persistent oliguria will eventually lead to volume derange-ments. Oliguria can be converted to a non-oliguric state by using diuretics and low-dose dopamine, liberating valuable time prior to commencing renal replacement ther-apy. There is, however, little evidence to suggest that these two agents improve renalrecovery times; ultimately, this depends on the number of remaining functional neph-rons increasing their filtration to maintain GFR. In the postpartum patient, oliguria may

Table 7. Aetiology of acute kidney injury.

Pre renal Intrinsic renal Post renal

Hypovolaemia

(e.g. sepsis, haemorrhage)

Inflammatory

(eg anti-GBM (glomerular basement membrane)

disease, ANCA-associated GN, SLE)

Urolithiasis

Low cardiac output states

(e.g. heart failure)

Thrombotic

[e.g. DIC, thrombotic micro-angiopathy

(TTP, HUS), antiphospholipid syndrome]

Blood clot

Pre-eclampsia and

HELLP syndrome

Interstitial nephritis (e.g. infections, drugs),

pre-eclampsia and HELLP syndrome

Urethral stricture

ANCA, antineutrophil cytoplasmic antibody; GBM, glomerular basement membrane; GN, glomerulone-

phritis; SLE, systemic lupus erythematosus; DIC, disseminated intravascular coagulation; TTP, thrombo-

cytopenic purpura; HUS, haemolytic uraemia syndrome; HELLP, haemolysis–elevated liver enzymes–low

platelets.


be normal, and, as described above, inappropriate intravenous fluids can precipitateiatrogenic pulmonary oedema. Lower targets for urine output are thereforeappropriate.

Metabolic derangements are an important aspect of AKI management. Hyperkalae-mia is best managed by limiting potassium input, augmenting elimination with diuretics,and promoting cellular uptake with insulin and glucose boluses. Severe acidosis (pH<7.2) may require treatment with sodium bicarbonate, although avoiding hypernatrae-mia and excessive volume expansion. The intracellular acidosis that follows should beremembered, although it is not a problem if the spontaneously breathing patient is ableto ‘blow off’ the CO2 or if the patient is being adequately mechanically ventilated.

The indications for renal replacement therapy are the same in pregnancy as for thegeneral population, but it is rarely required (<1 in 10 000–15 000 pregnancies). Thereis no clear evidence guiding dialysis dose prescription in AKI. Pregnant chronic dialysispatients achieve better fetal outcomes at higher dialysis doses (usually >20 h/week)compared with the standard regimen of 4 h thrice weekly.62 GFR is higher in preg-nancy so the goal should be to avoid under-dialysing these patients. The aim is formore frequent and longer dialysis sessions if using haemodialysis, and in the ICUsetting, continuous haemofiltration should be >35 mL/kg/h.

Hypothalamic pituitary adrenal function in critical illness

Hypothalamic pituitary adrenal function during critical illness is important and hasbeen shown to affect outcome in septic patients.63 Adrenergic receptor desensitiza-tion has been demonstrated with a reduction in alpha- and beta-adrenergic receptors.Steroids have been shown to help resensitize these receptors.

The evaluation of adrenal function during critical illness is controversial. Adrenal func-tion should still be tested, but commencement of steroid therapy should not be withhelduntil results are available.64 Currently, testing relies on random and low-dose Synacthen-stimulated serum total cortisol levels. In sepsis, adrenal insufficiency is likely when base-line cortisol levels are<10 mg/dL or the change in cortisol is<9 mg/dL, and unlikely whenthe Synacthen-stimulated cortisol level is �44 mg/dL or the change in cortisol is�16.8 mg/dL.9 Free cortisol or salivary cortisol when they become available will bemore useful. Plasma aldosterone and renin level are useful when primary adrenal diseaseis suspected, but pregnancy-specific normal ranges must be used.

When suspected, glucocorticoid doses should be physiological with either a contin-uous infusion of hydrocortisone or 4–6-hourly boluses with a daily dose �200 mg.This regimen should be discontinued once there has been clinical improvement.Such patients may include those requiring >24 h or an increasing dose of vasopres-sors, or those with diseases such as meningococcaemia.

Neurological management

Neurological support aims to relieve pain and anxiety. Sedation is usually required formechanical ventilation and invasive procedures. Agents include analgesics (paraceta-mol, opioids) and sedative-anxiolytics (benzodiazepines, propofol, haloperidol and clo-nidine). These are all used as needed, with consideration given to the implications onthe fetus. Intubation and some modes of ventilation may also require neuromuscularblockade. Daily sedation breaks are recommended to allow a circadian sleep–wake cy-cle and to re-assess neurology in these patients. Very agitated patients may need


sedation if intensive monitoring and treatment is required. ICU delirium is commonand difficult to manage.65

Investigations for coma would be as in the non-pregnant population with computedtomography þ/� magnetic resonance imaging, blood tests including cultures, lumbarpuncture if considering meningitis, encephalitis or demyelination, and urine for toxico-logical screening (Table 8). Electroencephalography can be useful to assess metaboliccoma and non-convulsive status, and hypoxic brain injury. Antidotes such as naloxoneand flumazenil may be needed but with consideration of the risk of precipitating sei-zures and fetal effects. Cases of poisoning or overdose should be discussed withthe local poisons unit.

For those with known epilepsy, the risk of seizures increases at the time of deliv-ery. For women at high risk for intrapartum seizures, intravenous phenytoin or rectalcarbamazepine can be given pre-emptively. In pre-eclampsia, the development of sei-zures defines eclampsia, and this is prevented and treated with magnesium sulphate.There are many other causes of seizures in pregnancy (including conditions listed inTable 8) as well as others including thrombotic thrombocytopaenic purpura) and ini-tial management focuses on resuscitation with control of fitting. Metabolic abnormal-ities including hypoglycaemia and hypocalcaemia should be corrected and intravenousmagnesium sulphate given, even without known pre-eclampsia; eclampsia may presentde novo. Further seizure management is with lorazepam or diazepam, then loadingwith intravenous phenytoin (20 mg/kg). Status epilepticus (seizures lasting >30 minor multiple seizures without regaining consciousness) is managed as outside preg-nancy, remembering the teratogenic effects of anticonvulsants during the first trimes-ter, and fetal respiratory effects if peripartum.

The use of mild therapeutic hypothermia following cardiac arrest is a fairly recenttreatment concept that followed two large multicentre randomized controlled trialspublished in 2002.66,67 It involves active cooling to 32–34

�C when return of sponta-

neous circulation (ROSC) follows a ventricular fibrillation or ventricular tachycardiaout-of-hospital arrest. The proposed mechanism is a reduction in cerebral metabolicrate which, with less free radical production and intracellular acidosis, is neuroprotec-tive.68 However, adverse events including arrhythmias, coagulopathy, immunoparesis,and abnormal blood glucose and acid–base control may occur, and its use in pregnancyhas not been reported to date.

Table 8. Causes of coma or collapse in pregnancy.

Intracerebral haemorrhage: arteriovenous malformation (AVM), Berry aneurysm, pre-eclampsia,

hypertension

Subarachnoid haemorrhage

Trauma: extradural or subdural haematoma

Prolonged hypotension or hypoxia

Embolic or ischaemic stroke, venous sinus thrombosis

Pituitary apoplexy

Brain structural abnormality, e.g. tumour

Infection: abscess, meningitis, encephalitis, septic encephalopathy

Demyelination

Metabolic: hypoglycaemia, hyponatraemia, acid-base disorders, rare causes (e.g. carbamyltransferase

deficiency)

Severe depression


Neurological intensive care

The principles of neurological intensive care management are similar to the non-preg-nant setting, with prevention of secondary brain injury following an initial insult. Theaetiology of most brain insults can be subdivided into those causing coma and thoseleading to traumatic brain injury (TBI); the leading cause of mortality in young people.Severe cases of TBI are best managed in major hospitals with neurosurgical andneuro-intensive care facilities.69 Management is as for the non-pregnant woman usingthe airways, breathing, circulation (ABC) approach (and cervical spine control) andconsideration for the fetus; immediate delivery may be indicated. Intubation andventilation is indicated when the Glasgow Coma Scale score is <8/15, or drops by2 points, or earlier depending on the pathology and management plan. In trauma,the secondary survey is essential in order not to miss other life-threateninginjuries.70

Prevention of secondary brain injury entails maintaining cerebral perfusion pres-sure (CPP) and normoglycaemia, and preventing complications such as infection.CPP depends on the pressure difference between MAP and intracranial pressure(ICP) within the rigid box that is the cranium (CPP¼MAP-ICP). ICP is usually<10 mm Hg; an ICP >20 mm Hg may distort cerebral architecture, reduce cerebralblood flow and lead to ischaemia and oedema. It is important to maintain MAP >80–90 mm Hg to maintain CPP in the non-obstetric population, and this target may belower in pregnancy.

Cerebral oedema may occur in TBI or other metabolic causes of coma due to dis-ruption of the blood–brain barrier, impaired mitochondrial ability to maintain normalionic cellular gradients, and ischaemia. ICP monitoring may be indicated, as the com-plication if left untreated is increasing pressure leading to coning and brain death. ICPmonitoring may be indicated and depends on local practice. Initial management forraised ICP is sedation, mannitol, moderate hyperventilation and cerebrospinal fluiddrainage. Further therapies include profound hyperventilation, barbiturate coma andsurgical decompression. In the obstetric patient, the effects of further hypocapniaare not clear. The diagnosis of brain death is no different to the non-pregnant patient,with considerations for perimortem caesarean section for fetal survival.71 Somaticsupport of a pregnant women following brain death is rare72, and organ support topreserve the fetoplacental unit must consider the predictable physiological changesthat occur following brain death. These include haemodynamic instability from the ex-cessive sympathetic discharge, panhypopituitarism, hypothermia, poor nutrition andinfectious complications.71

Haematological management

Haematological disorders are relatively common in pregnancy. Pregnancy is a thrombo-philic state with increased levels of most procoagulants that prevent excessive mater-nal blood loss at the time of delivery. This and the reduction in venous flow due to thegravid uterus leads to a five-fold increased risk of venous thromboembolism duringand immediately following pregnancy73, and is even higher in the puepurium.74 Preven-tion of venous thromboembolic events is therefore especially relevant in obstetrics.Prophylaxis with low-molecular-weight heparin (LMWH) or low-dose unfractionatedheparin, and the use of a mechanical intermittent compression device or compressionstockings is essential. The anticoagulant dose of LMWH is increased as glomerular fil-tration is elevated; for example, the dose of enoxaparin is 1 mg/kg bd, reverting to the


usual 1.5 mg/kg od dose following delivery.75 The prophylactic subcutaneous dose is40 mg/day in a normal-sized woman.

Anaemia is common in critical illness for many reasons. Blood transfusion targets inthe non-pregnant population are >7 g/dL, except in those with cardiac disease whoare kept >8 g/dL.76 Pregnancy targets should be similar, bearing in mind normal phys-iological anaemia.

Disseminated intravascular coagulation (DIC) is an acquired coagulopathy thatfollows a trigger of generalized coagulation activity. Other causes of coagulopathyare outlined in Table 9. In DIC, further consumption of platelets, clotting factorsand fibrin occurs, leading to a cycle of continuing bleeding and consumption of clot-ting components. In pregnancy, it should be anticipated from some of the associ-ated conditions such as massive obstetric haemorrhage (especially placentalabruption with direct exposure to fetal material), pre-eclampsia, retained fetal prod-ucts and amniotic fluid embolism. Sepsis is the most common overall cause in anyICU population, and other causes include transfusion reactions, trauma and drugs.Diagnosis is based on deranged clotting in an appropriate clinical setting with lowfibrinogen and elevated fibrinogen breakdown products (FDPs) or D dimer levels.Management is similar to that of major obstetric haemorrhage with prompt resus-citation and fluid replacement, with identification and treatment of the underlyingcause. Blood products need to be given as soon as available including packed redcells, fresh frozen plasma, cryoprecipitate and platelets. Recent developments in-clude recombinant activated factor VIIa (NovoSeven), originally used for haemo-philia and factor VII deficiency. It has been used for intractable blood loss andfulminant disseminated intravascular coagulation as it induces short-term local hae-mostasis. It has been used (off licence) with life-saving results in cases of massiveobstetric haemorrhage.77

NUTRITION AND GASTROINTESTINAL MANAGEMENT

Nutrition in pregnancy is important for the development of a healthy baby. Thegastrointestinal system is the portal through which macro- and micronutrients enter

Table 9. Causes of coagulopathy in pregnancy.

Obstetric causes Non-obstetric causes

DIC due to placental abruption,

placenta praevia, massive obstetric

haemorrhage, amniotic fluid embolus

DIC due to any other causes including

sepsis, trauma, incompatible transfusion reaction

Thrombocytopenia, e.g. HELLP syndrome,

TTP

Thrombocytopenia, e.g. ITP, sepsis, alcohol

Liver failure due to acute

fatty liver of pregnancy

Liver failure due to alcohol, paracetamol overdose etc.

Bone marrow failure due to effects of

shock (many causes)

Bone marrow failure or infiltration (many causes)

Pre-existing, e.g. haemophilia

Iatrogenic Hypothermia

DIC, disseminated intravascular coagulation; TTP, thrombocytopenic purpura; HELLP, haemolysis–

elevated liver enzymes–low platelets; ITP idiopathic thrombocytopaenic purpura.


the body. Proteins, fats and complex carbohydrates are digested, and vitamins, min-erals and water are absorbed across the gut mucosa. In pregnancy, there is an in-creased requirement for zinc, folate and vitamin B12 in the first trimester, andcalories in the second and third trimester. Nutritional support is required to meetthe increased metabolic demand and limited nutritional reserve during critical illness.However, despite extensive research, many areas in this field of critical care medicineremain controversial, due to a lack of well-controlled randomized trials.

The availability of functioning small bowel is vital and should prompt early feeding,preferably via the enteral route. Enteral nutrition is cheap and safe, but can be com-plicated by aspiration and poor gastric emptying, which results in poor absorption andunder-feeding. Increased progesterone levels in pregnancy cause smooth muscle relax-ation. This results in an increased likelihood of aspiration and constipation due to thereduced oesophageal sphincter tone and bowel peristalsis. Aspiration can be pre-vented by a 45

�head-tilt position and confirming the nasogastric tube placement ra-

diologically. Good absorption of feed often requires the use of prokinetic agents topromote gastric emptying when residual gastric volumes are high, and laxatives andenemas to prevent constipation. If poor absorption is a problem, drugs given via thenasogastric tube should also be considered to be poorly absorbed, and prompt con-version to the intravenous route should be instituted. Some drugs require enteral feedto be discontinued to ensure good uptake and effective absorption, such as the anti-convulsive drug phenytoin.

Protocols have been developed and are implemented by nurses to ensure that ad-equate enteral nutrition is delivered early and effectively. The failure to deliver 25% ofa patient’s calculated calorific requirement has been shown to result in increased mor-tality and infection rates.78 Protocol-directed regimens have been shown to reduce theincidence of under-feeding; however, it remains a significant problem for many patientsdue to frequent and often avoidable interruptions.

Total caloric requirements can be either estimated or calculated, and are often es-timated at 25–35 kcal/kg/day. Calculations are required at extremes of weight and per-formed by dieticians. The recommended nutritional requirements of a septic patientare 25 total kcal/kg/day, given in three forms: protein 1.3–2.0 g/kg/day; glucose30–70% of non-protein calories; and lipids 15–30% of non-protein calories.

The H2 receptor blocker ranitidine is used as prophylaxis against stress ulceration;there is no evidence to suggest that proton pump inhibitors are superior.79 The Na-tional Institute for Health and Clinical Excellence recommends that parenteral nutri-tion should be limited to 50% of the calculated calorific requirement, and it hasbeen shown to be less harmful than first thought. It is useful when the small bowelis being rested or not functioning for prolonged periods. Glycaemic control has alsobeen shown to affect outcome in sepsis, and the Surviving Sepsis Campaign guidelinesadvise controlling blood glucose <8.3 mmol/L. This should be achieved using insulininfusions and close monitoring of blood glucose.8

Micronutrients and electrolytes, e.g. magnesium, iron, copper, zinc and selenium,are necessary in small amounts. Phosphate is important since it is required for normalmetabolic processes resulting in the formation of ATP. Hypophosphataemia results inreduced contractility of skeletal muscles including respiratory muscles, which can leadto difficulties weaning from ventilatory support. Other micronutrients include fat-sol-uble (vitamins A, carotene) and water-soluble vitamins (vitamins B, C, D and E). Theprecise requirements for specific vitamins remain unclear, although several studieshave shown extremely low circulating concentrations. In pregnancy, the supplementa-tion of folate should be continued.


Early goal-directed therapy

Haemodynamic goal-directed therapy (GDT) was first used in sepsis and has sincebeen introduced in the peri-operative care setting, targeting oxygen delivery as the‘goal’. Original studies of sepsis in the late 1980s noted that survivors of sepsis hadsupranormal levels of oxygen delivery (DO2) compared with controls.80 However, tar-geting high DO2 levels did not initially appear to improve outcome.81 It became appar-ent from a meta-analysis of all the optimization trials that the timing of suchinterventions was crucial82 where the earlier interventions did in fact reduce mortality.There are evidently two phases to sepsis. The early phase is characterized by low ox-ygen delivery, high lactate and low SvO2 levels. This phase is associated with high mor-bidity and mortality if left untreated, but may be reversible if targeted early.83 Incomparison, the later phase of ‘established’ sepsis is more hyperdynamic with a higherSvO2, CO and DO2 (Table 10).84

This early work led to a landmark study of sepsis before admission to ICU. Riverset al studied patients with severe sepsis and septic shock over 6 h following presenta-tion to the emergency department (ED).10 Patients with systemic inflammatory re-sponse syndrome criteria and BP <90 mm Hg or serum lactate >4 mmol/L wererandomized to standard ED care or the early GDT protocol with continuous centralvenous oxygen saturations (ScvO2) monitoring with goals as follows: CVP 8–12 mm Hg, MAP> 65 mm Hg, urine output (UO)> 0.5 mL/kg/h, ScvO2> 70% (orSvO2> 65%). If the ScvO2 was below target, protocolized manouevres were under-taken to increase DO2. These included fluid boluses, giving packed cells to increasehaematocrit >30% and using vasopressors or inotropes. The other important featurein the trial was the use of antibiotics within 1 h. The overall results from the earlyGDT protocol indicted a significant mortality benefit (30.5% for early GDT vs46.5% for standard care). The important message from this is that survival in sepsisdoes appear to be influenced by the care in the first few hours, and that sepsis appearsto have an early reversible phase. It has revolutionized the importance of early diag-nosis and accessibility to critical care facilities for patients admitted with septic shockand severe sepsis. This principle has been extrapolated to the peri-operative care ofpatients.85

Cardiopulmonary resuscitation in pregnancy

Cardiac arrests in pregnancy are fortunately rare, occurring in approximately one in30 000 late pregnancies. They are less likely to have a primary cardiac cause compared

Table 10. Definitions of sepsis syndromes.83

Infection The inflammatory response to invasion of micro-organisms into normally sterile

host tissue

SIRS Response to a variety of clinical insults with more than two of: temperature <36�C

or >38�C; pulse >90 beats/min, respiratory rate >20/min; white cell count >12 or <4

Sepsis The systemic response to infection with more than two of the above SIRS criteria

Severe

sepsis

Sepsis with organ dysfunction, hypoperfusion or hypotension

(systolic blood pressure 40 mm Hg below baseline)

Septic shock Sepsis with hypotension despite adequate fluid resuscitation

SIRS, systemic inflammatory response syndrome.

Table 11. Causes of cardiac arrest in pregnancy.

Obstetric causes Non-obstetric causes

Pulmonary embolism Trauma

Amniotic fluid embolism Septic shock

Massive blood loss Drug overdose

Complications of pre-eclampsia

(and magnesium toxicity)

Acute myocardial infarction

Severe asthma

Uterine inversion Local anaesthetic toxicity

Aortic dissection Failed intubation, high spinal block


with cardiac arrests outside pregnancy. The most common reason for syncope is thesupine hypotension syndrome, and management of patients in the left lateral positionis essential. Other common causes of cardiac arrest in pregnancy are shown in Table 11.

The concept of a ‘chain of survival’ with basic and advanced life support is as impor-tant in pregnancy as in the general population. It includes early recognition and call forhelp, early cardiopulmonary resuscitation (CPR), early defibrillation and postresuscita-tion care. The structured ABC, airway-breathing-circulation approach in cardiac arrestunderpins the principles of basic and advanced life support with the goal of establishinga spontaneous return of circulation.

CPR in pregnancy is complicated by both physiological and physical changes that arewell established late in pregnancy. They affect the quality of CPR that can be delivered,and increase the possibility of complications. Each component is considered below, in-cluding the important differences in pregnancy.

Airway

Simple airway manoeuvres remain the same as for the general population. Difficult intu-bations are more common and effective pre-oxygenation is essential. Insertion of an ad-vanced airway at an earlier stage and with a 0.5–1 mm smaller endotracheal tube isrecommended. The short obese neck and full breasts make insertion of the laryngoscopemore problematic. Short-handled laryngoscopes, blades mounted greater than 90

�and

dismountable blades first inserted into the mouth can all help to overcome these difficul-ties. A laryngeal mask airway may be needed in cases of failed intubation, although cricoidpressure should be released and re-applied after insertion and inflation of the mask.

Breathing

Mouth-to-mouth and bag and mask ventilation should be performed without a pillowand the head fully extended. Ventilation can be hampered by flared ribs, raised dia-phragm, reduced chest compliance and difficulties seeing the chest rise. These alongwith greater oxygen demand and reduced FRC lead to rapid desaturation with inade-quate ventilation. The problems of ventilation can be compounded by aspiration,which is more likely in late pregnancy due to the incompetent gastro-oesophagealsphincter and raised intragastric pressure.

Circulation

Femoral intravenous access for resuscitation drugs is not advised, as central maternaldelivery will not occur until the fetus is delivered. Chest compressions should be


performed at the standard rate of 100/min and a ratio of 30:2. Hands should be po-sitioned further up the sternum because abdominal contents are displaced upwardsby the gravid uterus. The patient must be rolled into the left lateral position. Thisshould be up to 30

�or there is a tendency to roll into the full lateral position. This

angle is ideal for effective chest compression, and aids displacing the uterus off the in-ferior vena cava. This manouevre, along with raising the patient’s legs, will improve ve-nous return. One technique to achieve this is the ‘human wedge’, whereby the patientis tilted on to a rescuer’s knees to provide a stable position for CPR.

Defibrillation and drug administration is similar in pregnancy as for the general pop-ulation. Defibrillation will not deliver significant current to the fetus, but any fetal mon-itoring electrodes must be removed. Adhesive defibrillation pads have removed thedifficulties of applying the paddles in the correct position, normally affected by thefull breasts and left lateral position adopted. Excessive magnesium sulphate used totreat and prevent eclampsia can contribute to cardiac arrest. Empiric calcium shouldbe given and can be life saving.

Perimortem caesarean section

Failure to achieve ROSC after 5 min of CPR should prompt consideration of perimor-tem delivery. This should be considered by the team leader at the onset of cardiac ar-rest. The greatest chance of infant survival is in pregnancies >24 weeks of gestation asneonatal resuscitation can commence. It is obviously an aggressive procedure, but in-fant and maternal survival may depend on it. In pregnancies >20 weeks, emptying theuterus after this will improve CO by 60–80% of prepregnancy levels, allowing venousreturn and improving chances of ROSC, improving maternal and fetal outcome. Car-diac compressions are also more effective after delivery.86 In pregnancies <20 weeks,the gravid uterus is unlikely to have detrimental compressive effects. In pregnancies<23 weeks, infant survival is unlikely; if done, it should be for maternal survival.

Between 1975 and 2000, there were 56 postmortem caesarean deliveries with sixneurologically normal surviving infants (survival rate 10.7%). Eight infants were deliv-ered alive but died in the neonatal period. Of the 40 perimortem deliveries, 25 sur-vived neurologically intact (survival rate 62.5%).87

Post-resuscitation care

ROSC is an important step in resuscitation, but this must be followed by meticulouspostresuscitation care to increase the chance of a return to normal cerebral function.It focuses on the re-assessment of ABCDE to ensure good oxygenation, stable cardiacrhythm and BP. Once established, the patient can be transferred to a critical care areafor ongoing postresuscitation care.

SUMMARY

It is important to understand the aims of managing critically ill obstetric patients inmany areas of clinical medicine, surgery and anaesthesia. The most common reasonsfor UK obstetric ICU admissions are pre-eclampsia, sepsis and haemorrhage. The ma-ternal physiological differences make a significant impact on the assessment and man-agement, and must be considered at all times, especially the supine hypotensionsyndrome in positioning and resuscitation scenarios. Additional considerations arefor fetal wellbeing and appropriateness for delivery, which may be life saving for the


mother. The developments and trials in critical care medicine over the last 50 yearshave not included obstetric patients specifically. However, with the changes in mater-nal physiology borne in mind, there are no reasons why the principles should differgreatly. When considering haemodynamic management, the requirement for a highmaternal CO should be remembered. The low colloid oncotic pressure leads to anincreased tendency to develop iatrogenic pulmonary oedema, and several obstetric pa-thologies tend to increase alveolar capillary permeability, compounding the problem.Oliguria post delivery, especially in pre-eclampsia, should not usually be managedwith a fluid challenge. Airway management may be challenging with altered anatomy

Practice points

General supportive care� immediate resuscitation of the mother is paramount for maternal and fetal

survival� consider fetal age at an early stage; monitoring/assessment and delivery if

indicated� early identification of warning signs of critical illness� always plan in advance with the multidisciplinary team, where possible, such as

booking an ICU bed for expected high-risk deliveries

Haemodynamic management� remember the supine hypotension syndrome� beware of iatrogenic pulmonary oedema with fluid challenges� labour is a high-risk time for cardiac patients, with fluid shifts for up to 72 h

post partum

Cardiopulmonary resuscitation� airway: pregnant women may be very difficult to intubate (need skilled anaes-

thetist). Need smaller endotracheal tube, short-handled laryngoscope bladeand ‘difficult intubation’ equipment� breathing: may be difficult to ventilate. Increased risk of gastric acid aspiration� circulation: always use lateral position to avoid the supine hypotension syn-

drome. CPR cycles and drugs given as outside pregnancy, remembering thatMgSO4 toxicity can lead to cardiac arrest (give empiric calcium intravenously)� perimortem caesarean section may be necessary and should be considered at

the start of CPR

Research agenda

� more on the mechanism of ARDS in pre-eclampsia, and how to avoid iatro-genic pulmonary oedema� ideal ventilatory targets throughout pregnancy� short-term effects of fetal hypoxia, hypercapnia and acidosis


and high oxygen consumption, and rapid oxygen desaturation may occur. Ventilatorymanagement may be difficult for this reason and higher pressures may be needed.Some of the recommended ARDS ventilatory strategies are probably not appropriateas fetal haemoglobin binds oxygen less well when acidotic. Overall, critical care man-agement in obstetrics is mostly similar to a non-obstetric setting, applying the changesin maternal and fetal physiology in each case. High-risk patients should be identifiedearly, with appropriate planning and involvement of the multidisciplinary team.

ACKNOWLEDGEMENTS

The authors would like to thank Dr John Dick, consultant anaesthetist, for his helpfulcomments.

REFERENCES

1. Lewis G (ed.). The Confidential Enquiry into Maternal and Child Health (CEMACH). Saving Mothers’ Lives:

Reviewing Maternal Deaths to Make Motherhood Safer, 2003–2005. The Seventh Report on Confidential En-

quiries into Maternal Deaths in the United Kingdom. London: CEMACH, 2007.

2. Butwick AJ & Carvalho B. Can we improve maternal outcome for high-risk obstetric patients? Int J Ob-

stet Anesth 2007; 16: 311–313.

3. Maine D & Chavkin W. Maternal mortality: global similarities and differences. J Am Med Womens Assoc

2002; 57: 127–130.

4. Baskett TF & Sternadel J. Maternal intensive care and near-miss mortality in obstetrics. Br J Obstet Gy-

naecol 1998; 105: 981–984.

5. Kilpatrick SJ & Matthay MA. Obstetric patients requiring critical care. A five-year review. Chest 1992;

101: 1407–1412.

*6. Dellinger RP, Carlet JM, Masur H et al. Surviving Sepsis Campaign guidelines for management of severe

sepsis and septic shock. Crit Care Med 2004; 32: 858–873.

7. Bernard GR, Vincent JL, Laterre PF et al. Efficacy and safety of recombinant human activated protein C

for severe sepsis. N Engl J Med 2001; 344: 699–709.

8. Mebis L, Gunst J, Langouche L et al. Indication and practical use of intensive insulin therapy in the crit-

ically ill. Curr Opin Crit Care 2007; 13: 392–398.

9. Annane D, Maxime V, Ibrahim F et al. Diagnosis of adrenal insufficiency in severe sepsis and septic

shock. Am J Respir Crit Care Med 2006; 174: 1319–1326.

*10. Rivers E, Nguyen B, Havstad S et al. Early goal-directed therapy in the treatment of severe sepsis and

septic shock. N Engl J Med 2001; 345: 1368–1377.

11. Robson SC, Boys RJ, Hunter S et al. Maternal hemodynamics after normal delivery and delivery com-

plicated by postpartum hemorrhage. Obstet Gynecol 1989; 74: 234–239.

12. Capeless EL & Clapp JF. When do cardiovascular parameters return to their preconception values? Am J

Obstet Gynecol 1991; 165: 883–886.

13. Uebing A, Steer PJ, Yentis SM et al. Pregnancy and congenital heart disease. BMJ 2006; 332:

401–406.

14. Bakker J, Gris P, Coffernils M et al. Serial blood lactate levels can predict the development of multiple

organ failure following septic shock. Am J Surg 1996; 171: 221–226.

15. Spodick DH. Frank-Starling effect. Circulation 1979; 60: 718–719.

16. Oian P, Maltau JM, Noddeland H et al. Oedema-preventing mechanisms in subcutaneous tissue of nor-

mal pregnant women. Br J Obstet Gynaecol 1985; 92: 1113–1119.

17. Clark SL, Cotton DB, Lee W et al. Central hemodynamic assessment of normal term pregnancy. Am J

Obstet Gynecol 1989; 161: 1439–1442.

18. Reid F, Lobo DN, Williams RN et al. (Ab)normal saline and physiological Hartmann’s solution: a random-

ized double-blind crossover study. Clin Sci (Lond) 2003; 104: 17–24.


19. Barrett NA & Kam PC. Transfusion-related acute lung injury: a literature review. Anaesthesia 2006; 61:

777–785.

20. Vincent JL & Weil MH. Fluid challenge revisited. Crit Care Med 2006; 34: 1333–1337.

*21. Masip J, Roque M, Sanchez B et al. Noninvasive ventilation in acute cardiogenic pulmonary edema: sys-

tematic review and meta-analysis. JAMA 2005; 294: 3124–3130.

22. Peter JV, Moran JL, Phillips-Hughes J et al. Effect of non-invasive positive pressure ventilation (NIPPV) on

mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis. Lancet 2006; 367:

1155–1163.

23. Masip J, Paez J, Merino M et al. Risk factors for intubation as a guide for noninvasive ventilation in

patients with severe acute cardiogenic pulmonary edema. Intensive Care Med 2003; 29: 1921–

1928.

24. Follath F, Cleland JG, Just H et al. Efficacy and safety of intravenous levosimendan compared with dobut-

amine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet

2002; 360: 196–202.

25. Benlolo S, Lefoll C, Katchatouryan V et al. Successful use of levosimendan in a patient with peripartum

cardiomyopathy. Anesth Analg 2004; 98: 822–824.

26. Gowda RM, Khan IA, Mehta NJ et al. Cardiac arrhythmias in pregnancy: clinical and therapeutic con-

siderations. Int J Cardiol 2003; 88: 129–133.

27. Mercier FJ, Bonnet MP, De la Dorie A et al. Spinal anaesthesia for caesarean section: fluid loading, va-

sopressors and hypotension. Ann Fr Anesth Reanim 2007; 26: 688–693.

28. Dunser MW, Mayr AJ, Ulmer H et al. The effects of vasopressin on systemic hemodynamics in catechol-

amine-resistant septic and postcardiotomy shock: a retrospective analysis. Anesthesia and Analgesia

2001; 93: 7–13.

29. Krejci V, Hiltebrand LB, Jakob SM et al. Vasopressin in septic shock: effects on pancreatic, renal and

hepatic blood flow. Crit Care 2007; 11: R129.

*30. Beale RJ, Hollenberg SM, Vincent JL et al. Vasopressor and inotropic support in septic shock: an evi-

dence-based review. Crit Care Med 2004; 32(Suppl.): S455–S465.

31. Koonin LM, MacKay AP, Berg CJ et al. Pregnancy-related mortality surveillance – United States, 1987–

1990. MMWR CDC Surveill Summ 1997; 46: 17–36.

32. Magee LA, Cham C, Waterman EJ et al. Hydralazine for treatment of severe hypertension in pregnancy:

meta-analysis. BMJ 2003; 327: 955–960.

33. Cooper WO, Hernandez-Diaz S, Arbogast PG et al. Major congenital malformations after first-trimes-

ter exposure to ACE inhibitors. N Engl J Med 2006; 354: 2443–2451.

34. Catanzarite V, Willms D, Wong D et al. Acute respiratory distress syndrome in pregnancy and the pu-

erperium: causes, courses, and outcomes. Obstet Gynecol 2001; 97: 760–764.

35. Campbell LA & Klocke RA. Implications for the pregnant patient. Am J Respir Crit Care Med 2001; 163:

1051–1054.

*36. Cole DE, Taylor TL, McCullough DM et al. Acute respiratory distress syndrome in pregnancy. Critical

Care Medicine 2005; 33(Suppl.): S269–S278.

37. Izci B, Riha RL, Martin SE et al. The upper airway in pregnancy and pre-eclampsia. Am J Respir Crit Care

Med 2003; 167: 137–140.

38. Ezri T, Szmuk P, Evron S et al. Difficult airway in obstetric anesthesia: a review. Obstet Gynecol Surv 2001;

56: 631–641.

39. Rocke DA & Scoones GP. Rapidly progressive laryngeal oedema associated with pregnancy-aggravated

hypertension. Anaesthesia 1992; 47: 141–143.

40. Izci B, Vennelle M, Liston WA et al. Sleep-disordered breathing and upper airway size in pregnancy and

post-partum. Eur Respir J 2006; 27: 321–327.

41. Sahin FK, Koken G, Cosar E et al. Obstructive sleep apnea in pregnancy and fetal outcome. Int J Gynae-

col Obstet 2008; 100(2): 141–146.

42. Hood DD & Dewan DM. Anesthetic and obstetric outcome in morbidly obese parturients. Anesthesi-

ology 1993; 79: 1210–1218.

43. Cedergren MI. Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol

2004; 103: 219–224.

44. Adams JP & Murphy PG. Obesity in anaesthesia and intensive care. Br J Anaesth 2000; 85:

91–108.


45. Plant PK, Owen JL & Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic

obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial.

Lancet 2000; 355: 1931–1935.

46. Garpestad E, Brennan J & Hill NS. Noninvasive ventilation for critical care. Chest 2007; 132:

711–720.

47. Tobin MJ. Advances in mechanical ventilation. N Engl J Med 2001; 344: 1986–1996.

48. Chastre J, Viau F, Brun P et al. Prospective evaluation of the protected specimen brush for the diagnosis

of pulmonary infections in ventilated patients. Am Rev Respir Dis 1984; 130: 924–929.

49. Fagon JY, Chastre J, Wolff M et al. Invasive and noninvasive strategies for management of suspected

ventilator-associated pneumonia. A randomized trial. Ann Intern Med 2000; 132: 621–630.

50. Seligman R, Meisner M, Lisboa TC et al. Decreases in procalcitonin and C-reactive protein are strong

predictors of survival in ventilator-associated pneumonia. Crit Care 2006; 10: R125.

51. Dodek P, Keenan S, Cook D et al. Evidence-based clinical practice guideline for the prevention of ven-

tilator-associated pneumonia. Ann Intern Med 2004; 141: 305–313.

52. Ely EW, Baker AM, Dunagan DP et al. Effect on the duration of mechanical ventilation of identifying

patients capable of breathing spontaneously. N Engl J Med 1996; 335: 1864–1869.

53. Griffiths J, Barber VS, Morgan L et al. Systematic review and meta-analysis of studies of the timing of

tracheostomy in adult patients undergoing artificial ventilation. BMJ 2005; 330: 1243.

54. Ware LB & Matthay MA. The acute respiratory distress syndrome. N Engl J Med 2000; 342: 1334–1349.

55. Slutsky AS. Lung injury caused by mechanical ventilation. Chest 1999; 116(Suppl): 9S–15S.

56. Dreyfuss D, Soler P, Basset G et al. High inflation pressure pulmonary edema. Respective effects of high

airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 1988; 137:

1159–1164.

57. Tremblay LN & Slutsky AS. Ventilator-induced injury: from barotrauma to biotrauma. Proc Assoc Am

Physicians 1998; 110: 482–488.

58. Prakash J, Kumar H, Sinha DK et al. Acute renal failure in pregnancy in a developing country: twenty

years of experience. Ren Fail 2006; 28: 309–313.

*59. Gammill HS & Jeyabalan A. Acute renal failure in pregnancy. Crit Care Med 2005; 33(Suppl.): S372–S384.

60. Mehta RL, Kellum JA, Shah SV et al. Acute Kidney Injury Network: report of an initiative to improve

outcomes in acute kidney injury. Crit Care 2007; 11: R31.

61. Leanos-Miranda A, Marquez-Acosta J, Romero-Arauz F et al. Protein:creatinine ratio in random urine

samples is a reliable marker of increased 24-hour protein excretion in hospitalized women with hyper-

tensive disorders of pregnancy. Clin Chem 2007; 53: 1623–1628.

62. Barraclough K, Leone E & Chiu A. Renal replacement therapy for acute kidney injury in pregnancy.

Nephrol Dial Transplant 2007; 22: 2395–2397.

63. Arafah BM. Hypothalamic pituitary adrenal function during critical illness: limitations of current assess-

ment methods. J Clin Endocrinol Metab 2006; 91: 3725–3745.

64. Goodman S & Sprung CL. The International Sepsis Forum’s controversies in sepsis: corticosteroids

should be used to treat septic shock. Crit Care 2002; 6: 381–383.

65. Pun BT & Ely EW. The importance of diagnosing and managing ICU delirium. Chest 2007; 132: 624–636.

66. Safar PJ & Kochanek PM. Therapeutic hypothermia after cardiac arrest. N Engl J Med 2002; 346:

612–613.

67. Bernard SA, Gray TW, Buist MD et al. Treatment of comatose survivors of out-of-hospital cardiac

arrest with induced hypothermia. N Engl J Med 2002; 346: 557–563.

68. Busto R, Globus MY, Dietrich WD et al. Effect of mild hypothermia on ischemia-induced release of

neurotransmitters and free fatty acids in rat brain. Stroke 1989; 20: 904–910.

69. Patel HC, Bouamra O, Woodford M et al. Trends in head injury outcome from 1989 to 2003 and the

effect of neurosurgical care: an observational study. Lancet 2005; 366: 1538–1544.

70. Chesnut RM. Avoidance of hypotension: conditio sine qua non of successful severe head-injury manage-

ment. J Trauma 1997; 42(Suppl.): S4–S9.

*71. Mallampalli A & Guy E. Cardiac arrest in pregnancy and somatic support after brain death. Critical Care

Medicine 2005; 33(Suppl.): S325–S331.

72. Powner DJ & Bernstein IM. Extended somatic support for pregnant women after brain death. Critical

Care Medicine 2003; 31: 1241–1249.

73. Toglia MR & Weg JG. Venous thromboembolism during pregnancy. N Engl J Med 1996; 335: 108–114.


74. Refuerzo JS, Hechtman JL, Redman ME et al. Venous thromboembolism during pregnancy. Clinical

suspicion warrants evaluation. J Reprod Med 2003; 48: 767–770.

*75. Greer IA & Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of

venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 2005; 106:

401–407.

76. Hebert PC, Wells G, Blajchman MA et al. A multicenter, randomized, controlled clinical trial of trans-

fusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian

Critical Care Trials Group. N Engl J Med 1999; 340: 409–417.

77. Haynes J, Laffan M & Plaat F. Use of recombinant activated factor VII in massive obstetric haemorrhage.

Int J Obstet Anesth 2007; 16: 40–49.

78. O’Leary-Kelley CM, Puntillo KA, Barr J et al. Nutritional adequacy in patients receiving mechanical

ventilation who are fed enterally. Am J Crit Care 2005; 14: 222–231.

79. Brett S. Science review: the use of proton pump inhibitors for gastric acid suppression in critical illness.

Crit Care 2005; 9: 45–50.

80. Shoemaker WC, Appel PL, Kram HB et al. Prospective trial of supranormal values of survivors as ther-

apeutic goals in high-risk surgical patients. Chest 1988; 94: 1176–1186.

81. Gattinoni L, Brazzi L, Pelosi P et al. A trial of goal-oriented hemodynamic therapy in critically ill patients.

SvO2 Collaborative Group. N Engl J Med 1995; 333: 1025–1032.

82. Kern JW & Shoemaker WC. Meta-analysis of hemodynamic optimization in high-risk patients. Crit Care

Med 2002; 30: 1686–1692.

83. Parrillo JE, Parker MM, Natanson C et al. Septic shock in humans. Advances in the understanding of

pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med 1990; 113: 227–242.

84. Silance PG & Vincent JL. Oxygen extraction in patients with sepsis and heart failure: another look at

clinical studies. Clin Intensive Care 1994; 5: 4–14.

85. Pearse R, Dawson D, Fawcett J et al. Early goal-directed therapy after major surgery reduces compli-

cations and duration of hospital stay. A randomised, controlled trial ISRCTN38797445. Crit Care 2005;

9: R687–R693.

86. Morris S & Stacey M. Resuscitation in pregnancy. BMJ 2003; 327: 1277–1279.

*87. Whitten M & Irvine LM. Postmortem and perimortem caesarean section: what are the indications?

J R Soc Med 2000; 93: 6–9.

Aims of Obstetric Critical Care Management

Documents

disseminated

amniotic uid

acute fatty

hypercapnic

cardiogenic

critical care

massive obstetric

critical care