Ministry of Public Heals Service of Ukraine «Ukrainian Medical Stomatological Academy»

«APPROVING» on the sitting of chair of and gynecology №1 of UMSA (protocol №8 from 28. 08. 20)

Acting manager of chair of obstetric and gynecology №1 professor ______A.M. Gromova

METHODICAL POINTING for the independent work of students for preparation to practical lesson

Educational subject Obstetric Modul № 2 Subject of lesson Intensive therapy and reanimation women with obstetrical Course V faculty International faculty (specialty “medicine")

Poltava – 2020 Intensive therapy and reanimation women with obstetrical bleeding

Amniotic fluid embolism is the emergency in which amniotic fluid, enters the stream of the mother to trigger a serious systemic inflammatory reaction. The incidence of this pathology varies from 1:8000 to 1:80.000 of deliveries and is accompanied by a high mortality (86,5%), and 25% of women die within the first hour. In the structure of maternal mortality accounts for 1,2-16,5%. Amniotic fluid embolism typically occurs during normal labor (70%), cesarean delivery (19%) or in the immediate (11%). The clinical picture is depended on the composition and speed of amniotic fluid entering to the blood stream of the mother. Pathological process that develops in the body is the result of an allergic reaction of the maternal organism to antigens of the amniotic fluid. The diagnosis of the amniotic fluid embolism is based on the assessment of clinical symptoms, lab tests and additional methods of examination. Two stages of the clinical course of amniotic fluid embolism are distinguished: 1 – circulatory collapse and cardiopulmonary insufficiency; 2 – and hemorrhage. Clinical signs: • fear; • anxiety, agitation; • chills and hyperthermia; • cough; • sudden pallor or cyanosis; • sharp chest pain; • dyspnoea, loud breath; • decrease in BP; • tachycardia; • or other injured sites; • clinical signs of DIC-syndrome following 30 min-3 hours after the onset of symptoms. Additional methods of examination: - ECG – sinus tachycardia, myocardial hypoxia, cor pulmonale (SIQIII, P- pulmonale); - X-ray changes are revealed immediately or in several hours after the embolism with the signs of interstitial pneumonitis, - microscopy of blood from the pulmonary artery reveals fetal epidermal cells. Differential diagnosis: - myocardial infarction: pain, irradiating to the left arm, rhythm disturbance, ECG changes that are not always recorded in the fresh infarction; - thrombotic pulmonary embolism: abruptness, sudden cyanosis, dyspnoea, headache, chest pain. Often occurs in compromised veins (varicosity, trombophlebitis, phlebitis), ECG dextrogram; - : (in clumsy manipulations during intravenous infusions); - Mendelson’s syndrome (bronchospasm in response of aspiration of the acid gastric contents into the lungs) is the acid aspiration hyperereth pneumonitis. It commonly occurs in the induction of anesthesia in full stomach, when vomiting masses enter the airway. Management: 1. During or labor: urgent delivery.

2. Treatment of hypoxia: 100% О2; ALV. 3. Treatment of hypotension and left heart failure (infusion of crystalloids + vasopressors). 4. Correction of coagulopathy (fresh frozen plasma or prothrombin concentrate, cryoprecipitate, or antithrombin concentrate, VIIa recombinant factor, if possible). 5. Treatment of hemorrhage (transfusion of packed RBC + thromboconcentrate). 6. Cardiopulmonary resuscitation in case of the onset of clinical death. 7. Timely and adequate surgical hemostasis.

Monitoring of the vital signs should include: - BP measurement every 15 min; - central venous pressure; - heart rate; - respiratory rate; - pulse oximetry; - ECG; - hourly dieresis and urinalysis; - thermometry; - chest X-ray; - , Ht; platelets; - coagulogram; - acid-base balance and blood gases; - biochemical blood test and electrolytes. Criteria for the intensive therapy effectiveness: - elimination of the signs of the peripheral vasospasm; - diuresis > 30 mL/h; - normalization of hemostasis; - stabilization of respiration (saturation is not less than 90%).

OBSTETRIC HEMORRHOHAGIC SHOCK Hemorrhagic shock is defined as the acute cardiovascular insufficiency due to obstetric hemorrhage that leads to disproportion of circulating blood volume

(CBV) to bloodstream capacity and disbalance between the tissue demand in О2 and its actual delivery (see table ).

Table Criteria for estimation of the hemorrhagic shock by severity.

Classification of the hemorrhagic shock Signs І ІІ ІІІ ІV Blood loss:mL 750-1000 1000-1500 1500-2500 >2500 Blood loss 15-20 21-30 31-40 >40 % CBV Blood loss 0,8-1,2 1,3-1,8 1,9-2,4 >2,4 % of the body weight Heart rate (bpm) 100-110 110-120 120-140 greater 140 Systolic BP, mm.Hg over 90 90-70 70-50 50 and lower Shock index 0,8-1,2 1,0-1,5 1,5-2,0 >2,0 Test «white spot», sec up to 2 greater 2 greater 3 not detected Respiratory rate 20-25 25-30 up to 40 greater 40 (per min) Diuresis ml/h 30-50 25-30 5-15 anuria Mental status normal agitated confused lethargic Stages of shock compensated mild moderate severe

Hemorrhage is considered massive if: o Blood loss is greater than 50% of CBV within 20 minutes; o Blood loss rate exceeds 150 mL/h; o Nongraded loss of over 1500-2000 ml of blood or 25-30% CBV Arterial hypotension is considered as the late and unreliable clinical symptom of the obstetric hemorrhagic shock. Due to the physiological hypervolemic autohemodilution in pregnant, the BP can remain stable until the volume of blood loss reaches 30%. Hypovolemia compensation in pregnant women is ensured, first of all, due to the activation of the sympathoadrenal system, revealed by vasoconstriction and tachycardia. Oliguria reveals early. General principles of the acute blood loss management: 1. Prompt arrest of the hemorrhage by the conservative or surgical methods. 2. Provision of adequate oxygenation. 3. Replacement of blood volume lost. 4. Prevention and treatment of coagulopathy. 5. Treatment of the organ dysfunction: – treatment of heart failure and prevention of renal failure; – correction of metabolic acidosis; – stabilization of cellular metabolism. 6. Early prevention of infection. Initial steps in the hemorrhagic shock: 1. Assessment of vital signs (heart rate, blood pressure, respiratory rate,). 2. Oxygenation over the intranasal catheters or nasofacial mask (10-15 l/min). 3. Set the cot’s feet side 15-20 degrees higher than the head side (Trendelenburg position) to increase the venous blood circulation. 4. Turn the pregnant woman to the left side to prevent the development of the aortocaval compression syndrome, limit the risk of aspiration in vomiting and secure an airway. 5. Catheterization of two peripheral veins with catheters of big diameter. In case of collapsed veins venesection of v.Brahialis or catheterization of the central vein are recommended. Catheterization of the third vein (one of them should be central) should be performed along with replacement of the blood volume lost! 6. Sampling of 20 ml of blood is made to determine the blood group and Rh- factor, cross compatibility; Lee-White test is performed and simultaneously the infusion of the balanced crystalloid solutions starts. 7. Urinary bladder catheterization is performed and minimal monitoring of the hemodynamic indices is made: pulse oximetry, blood pressure, heart rate. All measurement should be documented. Careful consideration of blood volume lost! Follow up management of the hemorrhagic shock 1. Stream intravenous infusion of balanced crystalloids (Sterofundin iso, Ringer’s solutions, (solutio Ringeri)) and colloids (Gelofusine). Infusion therapy starts from crystalloids, and, simultaneously, artificial colloids are infused over another venous access aimed at blood volume replacement. At the same time plasma of the same group should be ordered and refrozen, and prepare the packed RBC for infusion. 2. Fresh frozen plasma should be infused at the earliest possible time! 3. Hemotransfusion is not recommended if the blood loss is less than 1,5% of the body weight. Blood transfusion is performed in the blood loss greater than 1500 ml (1,5% of the body weight) in the signs of hemorrhagic shock or profuse not-arrested bleeding, or in previous anemia. 4. In sustained hypotony which fails to be corrected by the infusive therapy, vasoactive and inotropic agents are used: Dopamine (5-20 µg/kg/min), or adrenalin (0,02 – 0,2 µg/kg/min), or noradrenalin (0,02-0,5 µg/kg/min), or combination of both. 5. Hemorrhage is arrested by the conservative or surgical methods depending on the cause of the bleeding development. 6. The woman should be warmed up. Considering the big amount of solutions to be infused they should be also warmed to 36° C. 7. Inhalation of 100 % oxygen is continued, ALV on indications. Indications for artificial lungs ventilations (ALV):

- hypoxemia (PaO2 less than 60 mmHg in FiO2 greater 0,5); - respiratory rate is over 40 per minute; - blood loss of 3 % of body weight or greater than 35 mL/kg. 8. Laboratory tests: complete blood count, platelets count, blood clotting time, coagulogram (activated partial thromboplastin time (APTT), fibrinogen, prothrombin index), electrolytes. 9. Monitoring observation: noninvasive measuring of BP, heart rate, pulse oximetry, capillary blood saturation, ECG, thermometry, control of the hourly diuresis. In case of stage III-IV shock development central venous pressure is to be controlled. The volume of infusion-transfusion therapy for bleeding is calculated taking into account the volume of blood loss (see table 12). Table 12 Infusion-transfusion therapy of blood loss in obstetrics (O.M. Klygunenko, 2002) Blood loss volume Totel Infusion-transfusion media transfusion Cristalloids Colloids Blood products

mL % of % of volum (in Ringer’s Refortan Packed Fresh Albumin body CBV % to CBV solution, gelofusin RBC frozen 10% weight deficite lactate mL/kg mL/kg plasma mL mL/kg mL/kg 500 - 1-1,5 10 - 200-300 10-15 10 _ _ _ 1000,0 20 (up 2,5 L) 1000,0- 1,5-2,0 21-30 200 10 10 5 5-10 _ (up 3 L л) 1500,0 1500,0- 2,0-2,5 31-40 7 7 10-20 10-15 200 180 2000,0 (up 4 L) 2500,0- 2,5-3,6 41-70 7 10-15 30 15-20 200 170 3000,0 (up 5 L) 150 Up to 10 Up to 20 > 30 > 20 > 200 more more more (up 6 L) 3000,0 3,6 70 DISSEMINATED INTRAVASCULAR COAGULATION SYNDROME Definition. Disseminated intravascular coagulation syndrome (DIC) is a pathological syndrome characterized by the activation of the vascular-thrombocyte or coagulation hemostasis (external or internal), leading to blood clotting first into microcirculatory stream, blocks it with fibrin and cellular aggregates and in derangement of coagulative and anticoagulative systems looses the ability to clotting, revealed by profuse hemorrhage and development of multiple organ failure syndrome. Causative factors for DIC syndrome development in obstetrics: amniotic fluid embolism, shock (hemorrhagic, anaphylactic, septic), , severe preeclampsia, , sepsis, septic , massive blood transfusion syndrome, transfusion of incompatible blood, ; , cesarean section, extragenital diseases of the pregnant woman (heart disease, malignant tumors, diabetes mellitus, severe renal and hepatic diseases). DIC syndrome classification: by the clinical course:  fulminant: from 1-2 hours (e.g., amniotic fluid embolism) to 1 day (e.g., septic shock);  acute: from 1 day to 1 week (e.g., massive hemorrhage);  subacute: from 1 week to 1 month (sepsis, preeclampsia);  chronic: from 1 month to 1 year (malignant tumors, etc.). by the clinical stages: I – hypercoagulation; II – hypocoagulation without generalized activation of fibrinolysis; III - hypocoagulation with generalized activation of fibrinolysis; IV – complete incoagulability. Diagnosis A diagnosis of DIC syndrome is based on the analysis and estimation of the clinical condition, supported by relevant laboratory results, since they provide with early and objective detection and effective treatment. Assessment of the hemostasis (determination of the stage and severity of the process) and consideration of the clinical manifestations of DIC syndrome is essential in choosing the therapeutic approach, including the correction of homeostasis (see table 13).

Table 13. Major clinical and laboratory signs of DIC stages DIC stages Clinical and laboratory signs

Uterine blood is clotted on the 3rd min and faster. Venous blood clotting is normal.

Chronometric hypercoagulation. I - hypercoagulation Ethanol test (ЕТ) (+). Hyperaggregation of platelets. UterineAPACHE blood II < clotting20 poin ts.is prolonged > 10 min. II-hypocoagulation PetechialType I-II ARDS.hemorrhage. without generalized Chronometric hypercoagulation, clot is brittle activation of fibrinolysis APACHE II 20 - 25 points Type II - IV ARDS Uterine blood is not clotted.

Venous time is clotted very slowly; the clot is lysed III-hypocoagulation quickly. with generalized Mixed type of bleeding activation of fibrinolysis Chronometric hypocoagulation Total hemorrhage APACHE II 25 - 30 points Uterine and venous blood is not clotted Type II - IV ARDS IV-complete incoagulability Potential hypercoagulation is absent Marked chronometric hypocoagulation Laboratory diagnosticsAPACHE II > 30 points Lee-White clotting time.Type 1 ml III blood - IV ARDSis drawn into dry conic test tube (better if blood flows out from the needle freely) and the clotting time is measured on the 37°C. Activated coagulation time (ACT). Normal ACT is 2 - 2,5 min. Test shows the hyper- or hypocoagulation disorders and is used to control the heparin therapy. Activated partial thromboplastin (aPTT) (25 – 40 sec normal time) defines the deficiency of factors of the coagulation cascade, such as XII, XI, IX, VIII. In hypocoagulation the increase in aPTT is observed. Shortened aPTT is the indicative of hypercoagulation. Thrombin time (TT) (16 - 20 sec normal time) measures the rate of conversion of fibrinogen into fibrin. Prolonged TT is caused by hypofibrinogenemia, elevated plasma FDP or presence of direct anticoagulants. Prothrombin time (PT) (11 – 12 sec normal) measures the activity or deficiency of the prothrombin complex (V, VII, X, II). Prolonged prothrombin time in normal thrombin time indicates about the inhibition of the common pathway of coagulation, i.e., deficiency of the V and II factors. Plasma fibrinogen level (2,0 - 4,5 g/L normal). Lowering of the fibrinogen is observed in DIC syndrome progression. Fibrin degradation products (<20 mg/L normal). Their decrease indicates about progressing intravascular coagulation and activation of fibrinolysis. Platelet count (150,000 – 300, 000 х 109/L). Their lowering indicates about the depletion of the platelet link of hemostasis and development of consumption coagulopathy. Prevention of DIC syndrome - Timely assessment of blood loss, adequate recovery of the CBV by crystalloid and colloid solutions. - Proper use of drugs that induce thrombocytopenia or impair platelet function (heparin, rheoporyglukin, dipyridamol). - Surgical interventions on indications are preformed timely and completely (hysterectomy) and promptly. In continuing bleeding ligation of the iliac artery is advocated. Treatment - Etiotropic therapy; - syndrome therapy: support of the major parameters of the homeostasis; - correction of coagulation abnormalities.

Management 1. Treatment of the underlying disease that caused the development of DIC syndrome (surgery, drug and infusion therapy). 2. Local arrest of bleeding from the wound is performed in all cases. It can be reached by various methods and techniques: coagulation, ligation, tamponade, use of local hemostatic means. 3. Recovery of the blood coagulation potential and correction of consumption coagulopathy. - Fresh frozen plasma up to 15-20 ml/kg daily stream intravenously over 4-6 introductions. Fresh frozen plazma and platelets are indicated in case of the confirmed multifactorial deficiency of coagulation, associated with hemorrhage and/or DIC. Cryoprecipitate or fibrinogen concentrate can be indicated if plasma fibrinogen level is less than 1 g/L. - Platelet concentrate is used in case of platelets lowering less than 50 х 109/L. The platelet concentrate dose is dependent on clinical condition. Routine use of heparin should be avoided considering the rate of conversion of hypercoagulation into hypocoagulation and inability to clearly define the stage of DIC syndrome development. 4. Treatment of multiple organ failure syndrome. 5. Transfusion of warm donor blood in half a dose of blood lost volume can be considered in the extreme urgent cases (further progression of hypocoagulation, bleeding (Hb < 60 g/l, Ht < 0,25 l/l) in presence of the vital signs in compliance with the final decision of doctors, personal agreement of the patient or her relatives. Clinical Situational Tasks 1. A 32-year-old G2P1 at 28 weeks gestation presents to labor and delivery with the complaint of vaginal bleeding. Her vital signs are: blood pressure 115/67 mm Hg, pulse 87 beats per minute, temperature 37.0 C, respiratory rate 18 breaths per minute. She denies any contraction and states that the baby is moving normally. On ultrasound the placenta is anteriorly located and completely covers the internal cervical os. Which of the following would most increase her risk for hysterectomy? 2. 10 minutes after delivery a woman discharged placenta with a tissue defect 5х6 cm large. Discharges from the genital tracts were profuse and bloody. Uterus tonus was low, fundus of uterus was located below the navel. Examination of genital tracts revealed that the uterine , vaginal walls, perineum were intact. There was uterine bleeding with following blood coagulation. Your actions to stop the bleeding? 3. A 26 year old woman had the second labour within the last 2 years with oxytocin application. The child's weight is 4080 g. After the placent birth there were massive bleeding, signs of hemorrhagic shock. Despite the injection of contractive agents, good contraction of the uterus and absence of any cervical and vaginal disorders, the bleeding proceeds. Choose the most probable cause of bleeding? 4. A 34 y.o. woman in her 29-th week of pregnancy, that is her 4-th labor to come, was admitted to the obstetric department with complaints of sudden and painful bloody discharges from vagina that appeared 2 hours ago. The discharges are profuse and contain grumes. Cardiac funnction of the is rhytmic, 150 strokes in the minute, uterus tone is normal. The most probable provisional diagnosis will be? 5. A 32-year-old woman, gravida 5, para 2022, at 36 weeks of gestation with placenta previa presents to labor and delivery with vaginal bleeding. After evaluation, decision to proceed with a cesarean delivery was made. She has a history of two previous low transverse cesarean sections. Delivery by low transverse cesarean section is complicated by placenta accreta. Estimated blood loss was 3.7 L. The patient is at which risk ?