Other therapies Antihypertensive agents and \202 uid management should be instituted as f or any woman with severe pre-eclampsia. Hematological and biochemical investigations should be performed to monitor for other features of severe pre- eclampsia and HELLP. Prior to de livery, fetal monitoring should be instituted immediately from the time of convul- sion to monitor for signs of fetal distress. History and examination Eclampsia can occur with no previous indicators of pre- eclampsia. After a convulsion, it is important to question relatives about any history of neurological disease and of the occurrence of symptoms of severe pre-eclampsia. Neurological examinatio n should be performed at the ear- liest opportunity to exclude signs of cerebral haemor- rh age, and regular monitoring for hypertension, proteinuria and pulmonary oedema should begin . Delivery Fetal distress is common during a convulsion, and this may necessitate immediate o perative delivery under general anesthesia. However, if the fetal condition is acceptable, it may be possible to institute magnesium and antihyperten- sive therapy before delivery. P latelet and coagulation tests should be performed before regional anesthesia is used. Special investigations \200 The same hematological and biochemical tests used in severe pre-eclampsia should be perform ed. Radiology. A CT scan may be indicated to exclude cere- bral hemorrhage. This should be suspected if focal neu- rological signs are found or if persistent unconsciousness follows a convulsion. Fetal studies. Continuous cardiotocography should be instituted in antenatal women. Further reading Douglas KA, Redman CWG. Eclampsia in the United Kingdom. BMJ 1994; 309: 1395 \200\223400. Duly L. Which anticonvulsant for women with eclampsia? Evidence from the Collaborative ecla mpsia trial. Lancet 1995; 345: 1455 \200\22363. This page intentionally left blank 522 M DRESNER HELLP syndrome should be anticipated, and in advanced pregnancy it is advisable to proceed to early delive ry before serious coag- ulopathy develops. In early pregnancy, risks to the neonate are obv iously much increased by delivery, so sympathetic counseling is vital for both partners. HELLP stands for Haemolysis, Elevated Liver enzymes, and Low Platelets, and is a severe var iant of pre-eclampsia peculiar to humans. It occurs in 20% of cases of severe pre-eclampsi a, with a mortality of 1 \200\2233.5%. Its insidious presentation and potential for sudden exacerbation fre- quently catches clinicians unaware, and its management re- quires rapid, multidisciplinary input. 80% of cases present before term, but 1/3 of cases are identi \201 ed after delivery. Premature delivery contributes to the very high perinatal mortality associated with HELLP syndrome. Glucocorticosteroids Observations that glucocorticoids, given to stimulate mat- uration of the fetal lungs, were associated with improve- ment of some of the markers of HELLP syndrom e, led to several clinical trials and a Cochrane Review. Whilst no clear improvements in ma ternal and perinatal mortality were found, higher platelet count, reduced hospital stay and higher birth weight followed steroid therapy. Prednisolone has limited placental transfer, so for bene \201 ts to mother and fetus, dexamethasone or betamethasone should be used. Clinical features While only 10% of cases present before 27 weeks, most do so before 36 wee ks gestation. Symptoms and signs are common but non-speci \201 c, and do not \201 t the usual pattern of severe pre-eclampsia. In addition to this, hypertension and proteinuria ar e not necessarily severe. There is there- fore great potential for diagnostic delay while s imple malaise rapidly progresses to anemia, coagulopathy and hepatorenal failure. There is also considerable risk of iatro- genic problems, largely through \202 uid overload during the treatment of haemolysis, thrombocytopaenia, coagulopa- thy and hemorrhage. As a \201 nal insult, recovery after deliv- ery is much more protracted than simple pre-eclampsia, a nd indeed the condition may worsen for the \201 rst 48h. For example, women with a platel et count <50 x 109/l may take 11 days to achieve a count >100 x 109/l. Of all pre-eclamptic patients, HELLP syndrome women are the most likely to require critical care, including ren al sup- port and possibly ventilation. Fluid management Renal function is precarious, with the renal lesion of pre- eclampsia comp ounded by hepatic disease, third space losses and a high incidence of hemorrhage. However, pul- monary oedema is also commonly associated with HELLP. Careful \202 uid balance is th erefore essential, but it can be easily derailed by the combination of hematological de \201 - cits and hemorrhage. Fluid overload may necessitate early dialysis if pulmonary oede ma is to be averted, because the kidneys may not respond adequately to diuretics. In ante- natal women, pulmonary oedema can precipitate the need for urgent Cesarean delivery in the face of coagulopathy, and a spiral of decline from massive hemorrhage to multi- system fail ure. History and examination \200 Key points \200 Symptoms: malaise (90%), epigastric pain (90%), nausea and vomiting (50%), and \202 u-lik e symptoms. Signs: right upper quadrant tenderness (80%), weight gain and peripheral oedema (60%). Hypertension and proteinuria may be mild or even absent. Symptoms and signs are non-specific, so diagnosis depends on close attention and a low thre shold for fur- ther investigation. Anticipate and plan for exacerbation to hepatorenal fail - ure, hemorrhage and pulmonary oedema. The early input of senior hematology, critical care and renal support clinicians is vital. Special investigations There is disagreement over the speci \201 c hematological and bioch emical criteria for the diagnosis of HELLP, but trends are more important than absolute \201 gures. \200 Further reading Martin JN Jr, Blake PE, Lowry SI, et al. Pregnancy complicated by preeclamp sia \200\223eclampsia with the syndrome of hemolysis, ele- vated liver enzymes, and low pla telet count: How rapid is post- partum recovery? Obstet Gynecol 1990; 76: 737 \200\22341. Hematology. Haemolysis can be identi \201 ed with a blood smear, rising LDH and rising tot al bilirubin. A platelet count <100 x 109/l is an agreed diagnostic criterion of HELLP. As liver function deteriorates, coagulation tests will also become abnormal. All hematological problems can be exacerbated by hemorrhage and dilution with IV \202 uids. Biochemistry. The levels of AST and ALT used to de \201 ne raised liver enzymes vary widely between auth ors. Local laboratory normal values and trends should therefore be used. Serum albumin will also fall, especially in cases complicated by hemorrhage and multi-system failure. Matchaba P, Moodley J. Corticosteroids for HELLP syndrome in pregnancy. Cochrane Database S yst Rev 2004: (1): CD002076. Sibai BM, Mabie BC, Harvey CJ, et al. Pulmonary edema in sever e preeclampsia \200\223eclampsia: analysis of thirty-seven consecutive cases. Am J Obstet G ynecol 1987; 156: 1174 \200\2239. Sibai BM, Ramadan MK, Usta I, et al. Maternal morbidity and mortal- ity in 442 pregnancies with haemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gy necol 1993; 169: 1000 \200\2236. Management General High dependency care and regular fetal monitoring are required once HELL P syndrome is diagnosed. Deterioration This page intentionally left blank 524 A PINDER & M DRESNER Postpartum hemorrhage Major obstetric hemorrhage remains a leading cause of signi \201 cant maternal morbidity a nd mortality. The lat- est Con \201 dential Enquiry into Maternal and Child Health (CEMCH) revealed it to be the 2nd most common cause of direct maternal death, with a mortality rat e of 8.5/1 000 000 maternities (17 deaths in total). This is a >2-fold in- crease from prev ious reports, the largest increase occur- ring in deaths from postpartum hemorrhage (PPH). PPH complicates 5% of deliveries. May follow antepartum hemorrhage (APH), especially placental abruption or praevia. In these circumstances, it is often poorly tolerated, especially if the degree of APH has been unde restimated and the woman inadequately resuscitated. Management Early recognition of bleeding and mobilization of the team Multi-disciplinary te am working and communication are vital in the management of PPH. \200 Classi \201 cation 1 Primary PPH. This is blood loss of >500ml from the genital tract with in 24h of childbirth. Causes are discussed below. Call essential personnel once recognized: on-call and consultant anesthetist and obstetrici an, senior mid- wifery staff, labor ward operating department practi- tioner and theater st aff from outside of labor ward (for \200\230extra hands \200\231 and to bring equipment su ch as rapid infus- ers and cell savers), porters (for transportation of blood sam- ples, bl ood and blood products), hematology and blood transfusion staff (for analysis of blood samp les and rapid provision of blood and blood products) and consultant hematologist (for advic e regarding appropriate blood and product replacement). 2 Secondary PPH. This is abnormal bleeding between 24h and 6 weeks postpartum, usually due to retained prod- ucts of conception and/or infection. Causes Uterine atony \200 \200 Most common cause of PPH. Risk factors include previous history of PPH, large placental sit e (e.g. multiple pregnancy), long or precipitous labor, pro- longed oxytocin administration , grand multi-parity, macro- somia, polyhydramnios, retained products, inverted or ruptured uterus, drugs (volatile anesthetics, tocolytics). Not excluded by absence of bleeding per vaginum as the atonic uterus may accommodate >1l of blood. Incidence reduced by prophylacti c administration of oxytocic agents at delivery. Resuscitation and restoration of circulating blood volume Rapid and effective resuscitation , following the standard ABC (airway, breathing, circulation) approach. \200 High \202 ow oxygen through face mask to a patent airway. Intubate and ventilate if reduc ed level of consciousness. Insert at least 2 large bore IV cannulae (14 \200\22316G) and ta ke bloods for baseline U&E, FBC, coagulation screen, group and cross-match (>6 units). Head -down tilt to aid venous return. Restore circulating blood volume with warmed crystal- loid and colloids, given rapidly via a pressure device until blood products are indicated or av ailable. Vasoconstrictors may be necessary to maintain an ade- quate blood pressure. Red bl ood cell transfusion indicated if several litres of crystalloid or colloid given, estimated blood loss >1.5l, Hb <7g/dl or blood loss very rapid. Rapid provision of group-speci \201 c blood aided by antenatal screening of blood group and abnormal antibodies. Emergency gro up O Rhesus negative red cells from delivery suite blood fridge in life-threatening, dire e mer- gency or if patient \200\231s blood group not known. Give blood products sooner rather than later. Be guided by clinical situation and blood results, but do not allow these to d elay their administration. Give 2 adult thera- peutic doses of platelets and 4 units (15ml/ kg) of FFP for each 6-unit red cell transfusion or if indicated by abnormal blood results ( platelets <75 x 109/l in acutely bleeding patient, higher if known abnormal platelet func- tion, clotting deranged 1.5 \227 control). Cryoprecipitate if \201 brinogen <1g/l. Avoid hypothermia (fluid warmer, forced warm air device, high ambient temperature). Retained tissue \200 Retained products of conception, placental tissue or membranes. Cause bleeding themselves a nd uterine atony. Trauma \200 \200 May arise anywhere in the genital tract. Includes lacerations in the perineum, vagina, cerv ix or uterus following vaginal or operative delivery. Coagulopathy \200 \200 May be a cause or complication of PPH May be pre-existing or develop in pregnancy due to ma s- sive blood transfusion, HELLP, drugs or DIC (e.g. placental abruption, pre-eclampsia, am niotic \202 uid embolism (AFE), prolonged intrauterine death, massive transfusion). Clinical approach Blood loss is dif \201 cult to assess accurately and is commonly underes timated. It may be partially or completely con- cealed or a slow persistent trickle, which may go unnoticed for some time. \200 Pregnant woman tolerate blood loss very well. They a re usually young, \201 t and healthy, and the physiological changes of pregnancy mean tha t several litres of blood may be lost before the classical signs of hypovolaemia develop. H ypotension is a late and ominous sign. Appropriate monitoring \200 Uterine blood \202 ow at term of 20% cardiac output gives rise to potential for massive b lood loss. What appears to be initially inconsequential bleeding may progress rapidly to ma jor life-threatening hemorrhage that proves dif- \201 cult to correct. Standard monitoring including pulse, blood pressure, ECG, oxygen saturation, respiratory ra te, urine output and temperature. 525 CHAPTER 31.4 Postpartum hemorrhage Anti \201 brinolytic agents \200 Early invasive monitoring (arterial and CVP) if haemody- namically unstable, but without de laying resuscitation and de \201 nitive treatment. If coagulopathy, consider ultrasound gu idance or antecu- bital site for CVP line. Delegate someone to document observations, along with timings and interventions, such as drugs and \202 uid input and output. Consider ne ed for HDU/ICU. Tranexamic acid (cyklokapron ) up to 0.5 \200\2231g IV bolus up to 3 times a day, or aprot onin (Trasylol ) up to 2 000 000U bolus followed by infusion 50-100 000U/h. License suspen ded 2007. CEM/CMO/2007/23. Both inhibit \201 brinolysis by enzyme inhibition Limited case reports of successful use in obstetric hemorrhage Possible thromboembolism risk \200 Control of hemorrhage \200\224treat cause and resultant complications Exclude uterine atony . If the uterus fails to contract ade- quately and bleeding continues, massage the uterus t o stimulate contraction and consider bimanual uterine com- pression. Cell salvage techniques \200 Traditional concerns of iatrogenic AFE minimized by use of speci \201 c suction systems an d leucocyte depletion \201 lter. Avoids complications associated with blood transfusion. Consider in presence of life-threatening PPH when the rate of blood loss greatly exceeds th at at which homolo- gous blood can be supplied, and in the Jehovah \200\231s witness popula tion. \200 Oxytocic agents Consider if uterine massage fails, but remember will be of no bene \201 t if the hemorrhage is not due to atony, and may be harmful, as all have potentially serious side effects. \200 Recombinant factor VIIa (Novoseven ) \200 Prohaemostatic agent promoting local thrombin genera- tion at bleeding sites. Several case reports of its successful use \200\230off license \200\231 in obstetric hemorrhage. Should be used in combination with replacement of de \201 - cient red blood cells, clotting fact ors, \201 brinogen and platelets, and attention to general measures such as sur- gical ha emostasis, avoiding hypothermia and acidaemia. (Cannot work without \201 brinogen.) Uncer tainties remain about appropriate dosing regimens (possibly 90 \200\223100mcg/kg), how to m onitor its effects and potential complications (DIC or thromboembolism, especially in the p resence of sepsis). Oxytocin (Syntocinon ). Synthetic analog of oxytocin. Short half-life of 10min. Given as s low IV bolus of 5IU and/or by infusion (40IU in 500ml of normal saline over 4h). It causes vasodilatation, which is compensated for by large increases in cardiac output by healthy wo men. In the presence of hypovolaemia, compensation is pre- vented and fatal cardiovascular collapse can ensue. Ergometrine. Ergot alkaloid given as IV or IM injections of 125mcg up t o 500mcg. Smooth muscle constrictor causing increased uterine tone, peripheral and pulmo- n ary vasoconstriction, bronchospasm. Also severe nau- sea and vomiting. Avoid in pre-eclamps ia, asthma and some cardiac conditions. Carboprost (Haemobate ). Synthetic prostaglandin a na- logue given as a deep IM injection, or intramyometrially (but not licensed for this), a t a dose of 250mcg every 15min, up to a maximum of 2mg. It has potentially seri- ous side e ffects including bronchospasm, pulmonary oedema, hypertension and increased intrapulmonary shunting with hypoxia. General vs regional anesthesia \200 Regional anesthesia is usually the technique of choic e in obstetric patients because of the well documented risks associated with general anesth esia. An epidural top-up or single shot spinal is usually a safe and acceptable technique where P PH is not life-threat- ening and the mother is not severely hypovolaemic and/ or coagulopat hic. It may unmask hypovolaemia, due to the loss of compensatory vasoconstriction with the on- set of sympathetic blockade, especially when blood loss has been underestimated. Genera l anesthesia may be the technique of choice in the presence of severe, continuing blood los s, haemodynamic instability, life-threatening maternal compromise, coagu- lopathy or antici pated prolonged or difficult surgery. Caution with volatile anesthetics reducing uterine to ne. Be prepared for major blood loss whatever the mode of anesthesia. Surgical interventions \200\230examination under anesthesia \200\231 \200 Empty the uterus. Remove placenta or retained prod- ucts of conception. Aids uterine contra ction too. Repair of genital tract injury. Uterine tamponade. Intrauterine balloon catheter (e.g. Rusch balloon), uterine packing. Laparotomy. Compression of aorta to allow catch up for resuscitation, uterine haemostatic suture (e.g. B-Lynch suture), arterial ligation, rep air of bleeding post-lower segment Cesarean section, hysterectomy. \200 Radiological interventions \200 Further reading Department of Health. Con \201 dential Enquiry into Maternal and Child Hea lth. Why mothers die 2000 \200\2232. The sixth report of the con \201 dential enquiries in to maternal deaths in the UK. London RCOG Press, 2004. High success rates reported for uterine artery embolization. May avoid need for hysterectom y and preserve fertility. Practical difficulties include need for appropriately trained sta ff, equipment and facilities, and transfer of unstable patient to isolated radiology suite \200 Grady K, Howell C, Cox C. Managing obstetric emergencies and trauma. The MOET course manual , 2nd edn. London: RCOG Press, 2007. 526 A PINDER & M DRESNER Amniotic \202 uid embolism Amniotic \202 uid embolism (AFE) is a rare condition, with incidence varying between 1 in 8000 and 1 in 80 000 preg- nancies. This wide range re \202 ects the dif \201 culty in c on \201 rm- ing its accurate diagnosis. Despite its rarity, AFE remains a leading cause of maternal morbidity and mortality. The lat- est CEMCH report revealed it to be the 8th most common cause of direct maternal death in the UK, with a mortality rate of 2.5/1 000 000 ma ternities (5 deaths). The number of maternal deaths due to AFE has fallen signi \201 cantl y over the last 3 triennia, largely attributable to improved intensive care management and recognition of milder cases. All cases of suspected or proven AFE, whether fatal or not, sh ould be reported to the UK Obstetric Surveillance System (UKOSS). This national registry ai ms to study the incidence, risk factors, management and outcomes of AFE in the UK. Nineteen cases of AFE were reported to UKOSS during 2000 \200\2232002, giving a 25% mortality rate. Previous registries from the UK, the USA and Australasia, which have provided much of our current knowledge about AFE, reported much higher mortality rates of up to 80%, with only 1 5% of patients surviving neurologically intact . prognosis. Despite this, the most severe, fulminant end of the disease spectrum may prove r apidly fatal despite optimal management, many deaths occurring within an hour of presentati on. Diagnosis Clinical AFE exists as a spectrum of disease, ranging from a sub- clinical entity to a severe and rapidly fatal event. The initial diagnosis is usually made on clinical gro unds following the sudden onset of characteristic signs and symptoms as above. Histological Traditionally, AFE was a post-mortem diagnosis. Nowadays, the \201 nding of amniotic \202 uid debris (fetal squames, epithe- lial cells, mucin, lanugo) in maternal l ung tissue or pulmo- nary artery blood can be used to support the diagnosis of AFE, suspect ed on clinical grounds. These post-mortem \201 ndings alone, without a clinical suspicion of AFE, are no longer considered pathognomonic as small amounts of such elements can enter the maternal circulation without sequelae. Risk factors \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Investigations No speci \201 c investigation can con \201 rm the diagnosis of AFE, althou gh some may be useful for diagnosis and management. \200 \200 Increasing maternal age. Overactivity of the uterus/overuse of oxytocic drugs. Short and tu multuous labor. Multiparity. Large fetus. Increased gestational age. Placental abruption. I ntrauterine death. Uterine rupture. Trauma. ABG. Hypoxaemia and adequacy of ventilation. FBC and clotting pro \201 le. Diagnose DIC an d manage haem- orrhage and DIC. Serum tryptase CXR. Pulmonary oedema. ECG. RV strain, arr hythmias. TTE or TOE. Assessment of ventricular function. CVP/pulmonary artery catheter blo od sample. As with post-mortem, the presence of fetal squames and other debris supports a c linical diagnosis but is not pathogno- monic. \200 \200 \200 \200 Association of these risk factors with AFE has been incon- sistent. Many patients who devel op AFE have no risk fac- tors. The classical \200\230hypertonic \200\231 uterus may be the result of, rather than the precipitant of, AFE. Clinical features Classical \200\230triad \200\231 \200\224hypoxia cardiovascular collapse coagu- lopathy \200\224presenting during labor, delivery or 30min post- partum, with no ot her clinical condition to explain signs and symptoms. It has also been reported to occur du ring or after Cesarean section, amniocentesis, \201 rst and second trimester abortions, a bdominal trauma, arti \201 cial rupture of membranes and up to 48h postpartum. \200 Differential diagnosis AFE is a diagnosis of exclusion from other causes of mater- nal coll apse: \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Pre-eclampsia or eclampsia Pulmonary aspiration Pulmonary thromboembolism Placental abrupti on Air embolism Septic shock AMI Anaphylaxis Coagulopathy Uterine rupture Uterine atony and PPH CVA Anesthetic toxicity Acute hypoxia. Causes may be pulmonary vasospasm, ventilation \200\223perfusion mismatch, b ronchospasm or pul- monary oedema. This may present as cyanosis, dyspnoea, wheezing or resp iratory arrest. Acute cardiovascular collapse. Hypotension, dysrhyth- mias or cardiac arres t. Coagulopathy. If rapid onset and deterioration, DIC or clinical hemorrhage may not have time to develop. Less common presentations include chest pain, seizures, confusion and acut e fetal distress. The latest CEMACH report highlighted premonitory signs and symptoms such as restlessness, abnormal behavior and respiratory distress occurring before collapse and h emorrhage. Earlier suspicion of AFE may then permit earlier involvement of intensive care a nd an improved Pathophsiology AFE was classically attributed to amniotic \202 uid and debris entering th e maternal circulation. This needed a disruption of the normal barriers between amniotic \202 uid and the maternal venous circulation, and a pressure gradient allowing the entrance of amniotic \202 uid into the maternal circulation. 527 CHAPTER 31.5 Amniotic \202 uid embolism cyclin could be useful, but are unlikely to be available in the time they would potentially be bene \201 cial. As fetal squames can be detected in the maternal cir- culation in normal labor, without AFE developing, their mere presence \200\230plugging \200\231 the pulmonary vasculature canno t account for the syndrome that develops in some women. It is still unclear whether abnorma l factors in amniotic \202 uid, such as meconium, are responsible or whether the syn- dro me represents an anaphylactoid-type reaction to amni- otic \202 uid in susceptible indivi duals. The latter is supported by the similar clinical, hematological and haemodynamic dera ngements found in both AFE and anaphylactoid re- actions, suggesting common underlying path ophysiologic mechanisms, and a history of allergy and atopy in almost half of women who dev elop AFE. The variable clinical picture seen in response to fetal material in the mater- na l circulation would then be dependent on the nature and quantity of that material and the s usceptibility of the mother. A biphasic model has also been described. The initial phase de velops following the entry of amniotic \202 uid into the maternal circulation. Pulmonary vasospasm with acute pulmonary hypertension and right heart failure follow, causing severe hypoxia and a fall in cardiac output. This ini- tial phase is transient, lasting usually <3 0min, but the pro- found hypoxia that develops is responsible for most early AFE deaths and the permanent neurological impairment in survivors. During the secondary phase, RV functio n re- turns to normal but LV failure with pulmonary oedema and hypotension develop, seconda ry to hypoxia and direct depressant effects of amniotic \202 uid on the myocardium. Proco agulants in the amniotic \202 uid and widespread tissue hypoxia then trigger excessive co agulation in those women lucky enough to survive the initial insults. Circulation. Insert at least 2 large bore IV cannulae (14 \200\22316G) and take bloods for baseline U&E, FBC, coagulation screen (including \201 brinogen and D-dimers), tryptase, g roup and cross-match (>6 units). Maintain cardiac output with IV \202 uids and inotropes as required. Caution with \202 uid loading in the presence of right, then left ventricula r failure. Remember uterine displacement if antepartum. Standard monitoring including pulse , blood pressure, ECG, oxygen saturation, respiratory rate, urine output and temperature. E arly invasive monitoring (arterial and CVP, under ultrasound guidance) if haemodynamically unstable, but without delaying resuscitation and de \201 nitive treat- ment. Consider pulm onary artery catheter or TOE to guide \202 uid resuscitation. If maternal cardiac arrest, follow standard ALS algo- rithms, including perimortem Cesarean section within 5min. Corre ct DIC with red blood cells, FFP, cryoprecipitate and platelets, under the guidance of a co nsultant haema- tologist. Manage the predictable massive obstetric hemorrhage resulting fro m DIC and uterine atony. Caution with oxy- tocic agents (see Chapter 32.4). Delegate someon e to document observations, along with timings and interventions, such as drugs and \202 uid input and output. If survives, transfer to ICU. Further reading Burros A, Khoo S. The amniotic \202 uid embolism syndrome: 10 years exper ience at a major teaching hospital. Aust N Z Obstet Gynaecol 1995; 35: 245 \200\22350. Management No speci \201 c pharmacological or other therapies prevent or treat AFE. Manage ment is purely supportive to maintain oxygenation, restore normal blood pressure and cardia c output, and correct coagulopathy. \200 Clark SL, Hankins GDV, Dudley DA, et al. Amniotic \202 uid embolism: Analysis of the regi stry. Am J Obstet Gynecol 1995; 172: 1158 \200\22367. Department of Health. Con \201 denti al Enquiry into Maternal and Child Health. Why mothers die 2000-2. The sixth report of the con \201 dential enquiries into maternal deaths in the UK. London: RCOG Press, 2004. Call for help, including senior anesthetic, obstetric and midwifery colleagues. Inform ITU and hematologist. Rapid and effective resuscitation, following the standard ABC (airway, br eathing, circulation) approach. Airway and breathing. High \202 ow oxygen through face ma sk to a patent airway. Consider intubation and ventila- tion if reduced level of consciousn ess or severe hypox- aemia on ABG analysis. Oxygen is also an effective pulmonary vasodilat or for the management of pulmo- nary vasospasm, although the latter is usually only a tran- sient phenomenon. IV pulmonary vasodilators risk systemic vasodilatation and hypotension. NO or procta- Grady K, Howell C, Cox C. Managing obstetric emergencies and trauma. The MOET course manual , 2nd edn. London: RCOG Press, 2007. Tuffnell DJ. UK amniotic \202 uid register. Br J Obstet Gynaecol 2005; 112: 1625 \200\2239. UK Obstetric Surveillance System, National Perinatal Epidemiology Unit. Oxford. This page intentionally left blank 529 Chapter 32 Death and dying Chapter contents Con \201 rming death using neurological criteria (brainstem death) 530 Withdrawing and wit hholding treatment 532 The potential heart-beating organ donor 534 Non-heart-beating organ donation 538 530 I THOMAS & AR MANARA Con \201 rming death using neurological criteria (brainstem death) held open. There should be no eye movement, princi- pally nystagmus, during or after the in jection, and the eyes should be observed for 1min after each injection. Direct access to th e tympanic membrane must be con- \201 rmed on each side using an auriscope, and the head should be \202 exed at 30 to the horizontal plane. The diag- nosis is not invalidated i f it cannot be performed on one side due to localized trauma. There should be no gag reflex or cough reflex in response to a suction catheter being passed into the pharynx or down th e ETT to stimulate the carina. The brainstem provides the anatomical link between the spinal cord and cerebral hemispheres relaying sensory and motor impulses between the periphery and higher cortical centers. It also contains cranial nerve nuclei, the reticular activating system and cardiorespiratory c ontrol centers, the destruction of which underlies the process of con \201 rm- ing death a ccording to neurological criteria (brainstem death). Background Described in 1968 by the Harvard Medical Committee and adopted in the UK in 1976 following the Conference of the Royal Colleges and their Faculties, the permanent and irre - versible loss of all brainstem re \202 exes equates to the death of an individual, with the permanent functional death of the brainstem constituting brain death; a position since adopted by the courts of England and Wales. The UK guidelines have been most recently publi shed by the Department of Heath and Academy of Royal Medical Colleges in 2008. Apnoea testing The responsiveness of the respiratory system to hypercar- bia is the \201 nal test performed to con \201 rm brainstem death, and should not be performed if any of t he preceding tests con \201 rm the presence of brainstem function. It is recom- mended tha t end-tidal carbon dioxide (ETCO2) monitor- ing is utilized to minimize the risk of excessi ve hypercarbia and/or rapid changes in carbon dioxide tension, so limiting the risk of furt her injury to potentially recoverable brain tissue. The patient should be pre-oxygenated wi th 100% oxygen for 5min. With a SpO2 >95%, minute volume venti- lation is reduced and the E TCO2 allowed to rise slowly. Once the ETCO2 is >6.5kPa, a level high enough to exceed the n ormal threshold for stimulation of respiration, an ABG is taken to con \201 rm that the Pa CO2 is >6.5kPa. If car- diovascular stability is maintained, the patient should then be dis connected from the ventilator for 5min. Hypoxia is prevented by insuf \202 ating oxygen at 10l/min via a suction catheter placed down the ETT with continual SpO2 moni- toring. Whils t disconnected, the patient should remain apnoeic and is continually observed for any respi ratory effort (abdomen and chest exposed). If after the 5min there has been no spontaneous respiratory effort, a fur- ther con \201 rmatory ABG is taken. The ventilator should then be reconnected and the minute volume returned to the setting that allows blood gasses to re turn to the target value for the patient \200\231s further management. In patients with pre existing chronic respiratory disease who rely on a hypoxic drive to respiration, a mild b ut signi \201 cant acidosis should be achieved by allowing the PaCO2 to rise to a point wh ere the pH is <7.35. Etiology Brainstem death may follow a severe global insult such as hypoxia or a direct insu lt such as trauma or focal ischaemia resulting from vertebral/basilar artery pathology. The most common causes of brainstem death are traumatic brain injury, CVAs (including SAH), ce rebral tumors, meningitis and hypoxic brain injury. The process of con \201 rming death by neurological testing Pre-conditions Certain pre-con ditions must be met before neurological testing can be undertaken: \200 The cause of the coma must be established as an irre- versible structural cause of brain in jury. The patient must be deeply comatose, apnoeic and dependent on mechanical ventilation. The possibility of neuromuscular blockade should be excluded by means of a peripheral nerv e stimulator or the eliciting of deep tendon re \202 exes. Ventilatory depression due to d rugs or spinal cord injury must be excluded. The patient must be unresponsive with reversib le causes of brainstem depression excluded: hypothermia (<34 C), sedative drugs, alcohol, circulatory, endocrine and meta- bolic disturbances. Deviations outside normal values that are clearly a consequence of brainstem death rather than its cause do not preclude the diag nosis. Timing of testing Testing should not be considered until at least 6h after the onset of apn oeic coma or, if the cause is presumed to be hypoxic injury following cardiac arrest, many would allow a minimum of 24h after the restoration of the circulation. Establishing the irreversible loss of brainstem re \202 exes This may only take place in a setting where the above pre- conditions have been met \200 Conduct of testing Neurological testing to confirm death should be per- formed by two medic al practitioners both of whom should have held full registration with the General Medical C ouncil for at least 5yrs. One should be an ICU consultant or the consultant in charge of th e patient, and both should be competent in the procedure. Neither should have any con- nect ion to the transplant team. The doctors may perform the tests independently or together. Th ere is no statutory time interval that must pass between the two sets of tests; it is a mat ter of clinical judgment to decide when suf \201 - cient time has elapsed between tests to satisfy all those involved. Two sets are undertaken to remove the risk of observer error a nd to reassure the family. The pupils are fixed with no direct or consensual response to light. The pupils need not be dilated or equal in size and shape for the diagnosis to be con \201 rmed. The corneal re \202 ex is absent. There is no motor response within the cranial nerve dis- tribution to a painful stimulus applied centrally or periph- erally. Spinal re \202 exes may persist in brainstem dead patients. The oculovestibular (caloric) re \202 ex is absent. This is perfo rmed by injecting 50ml of ice-cold water over 1min into each external auditory meatus whils t the eyelids are \200 531 CHAPTER 32.1 Con \201 rming death using neurological criteria (brainstem death) Other considerations \200 thiopenton,e can be said to be negligible following pro- longed administration. No speci \201 c ranges can be set within which biochemical variables must fall to be considered \200\230normal \200\231 and com- patible with brainstem death testing, although recom- mend ations as such have been made by the Academy of Royal Medical Colleges. Death may be con \201 rmed after completion of the second set of tests. The time of death is then recorded as the time at which the \201 rst set of tests was completed. Documentat ion of the results should be on the appro- priate form approved by the UK Department of Hea lth. The coroner should be informed of most of these patients due to the underlying diagnos is, mechanism of injury or if organ donation is to take place. Effective communication with relatives enables under- standing of the indications for and components of brain- stem dea th testing and its implications, and may help to alleviate emotional distress. Subsequent actions After the neurological con \201 rmation of death, subsequent actions de pend on whether the patient had expressed a wish to donate their organs after death. If so, the mainte- nance of normal physiological parameters is vital to ensure optimal organ viab ility. This includes correcting the physio- logical consequences of brainstem death includi ng cardio- vascular instability (hypotension and arrhythmias), hypothermia, diabetes insipi dus, DIC, hyperglycaemia, acidosis and other metabolic and endocrine abnormalities. If dona tion is not an option, then following consultation with the relatives, withdrawal of respir atory support may take place at a time acceptable to all parties. Ancillary tests No additional tests are required in the UK to con \201 rm brainstem death, although ancillary tests such as four-ves- sel cerebral angiography, transcranial Doppler or radioiso- tope scanning may be used to establish the absence of CBF in cases of diagnost ic uncertainties. EEG or brainstem evoked potential testing are not usually helpful in esta blish- ing the diagnosis. Further reading Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. A definition of irreversible coma. JAMA 1968; 205: 337 \200\223 40. Problems \200 Depending on the underlying pathology, there may be uncertainty as to when the brain injury can be consid- ered irreversible and brainstem testing can take place. With altered pharma cokinetics in critically ill patients, uncertainty may surround the length of time that has to elapse before the effects of sedative agents, e.g. Conference of the Medical Royal Colleges and their Faculties in the United Kingdom. Diagnos is of brainstem death. BMJ 1976: 1187 \200\2238. Department of Heath and Academy of Royal Medical Colleges. A code of practice for the diagnosis of death. 2008. 532 C DANBURY Withdrawing and withholding treatment