9/16/2012. Progression of Shock. Blood pressure: Pathophysiology & Clinical Management

Transcription

1 Mean BP (mm Hg) 9/16/212 September 2, 14: 6 min Blood pressure: Pathophysiology & Clinical Management Shahab Noori, MD Associate Professor of Pediatrics Division of Neonatology Progression of Shock BP maintained Hypotension Multiorgan failure Insult Compensated shock Uncompensated shock Irreversible shock Rationale for recognition and treatment of hypotension: a) Prevention of progression of shock to irreversible stage b) Association with brain injury and poor developmental outcome Gestational- and Postnatal-Age Dependence of BP Lower Limit of the 8% Confidence Interval of BP in Neonates ( First 3 Postnatal Days) weeks weeks weeks weeks Age (h) * = 9% of neonates will have a mean BP value at or above the lower limit of the confidence interval 1. Nuntnarumit et al, Clin Perinatol; 1999:26:981 1

2 9/16/212 Definition of Hypotension in the VLBW Neonate Hypotension has been defined as 1 : a) Mean BP (mmhg) < gestational age (wks) b) Mean BP 5th (1th) percentile for gestational and postnatal age c) Mean BP < 28-3 mmhg d) Permissive Hypotension with no defined value 1. Noori S. et al. Clin Perinatol 29;36: Blood Flow vs. Blood Pressure Poiseuille s Law: P 1 P 2 Q = P x r 4 8 l r l Ohm s Law: Q = P R Q = flow P = pressure gradient = 3.14 r = radius = viscosity l = length R = resistance Ohm s Law: Blood Flow vs. Blood Pressure Q = P R Cardiac Output = Blood Pressure Peripheral Vascular Resistance Blood Pressure = Cardiac Output x Peripheral Vascular Resistance Cardiac Output Blood Pressure = 2 x Peripheral Vascular Resistance x 2 2

3 9/16/212 PRINCIPLES OF CARDIOVASCULAR PHYSIOLOGY: BLOOD PRESSURE, BLOOD FLOW, BLOOD FLOW DISTRIBUTION, VASCULAR RESISTANCE When OBF regulation exhausted: 1. Capillary recruitment 2. O 2 extraction Vital organ blood flow distribution (brain, heart, adrenals) Systemic Flow Independent variable (Inotropes) Systemic Blood Pressure Dependent Variable O 2 Delivery to Meet O 2 Demand BP = CO x SVR Resistance affected by: 1. Autonomic, endocrine, paracrine, autocrine regulators of vascular function 2. GA, PNA, shunts, vascular anatomy 3. ph, PaCO 2, PaO 2, electrolytes (Ca ++ i) Pathology: cytokines, chemokines Systemic Resistance Independent variable (Vasopressors, Lusitropes) Systemic blood flow affected by 1. Autonomic, endocrine, paracrine, autocrine regulators of cardiac function 2. GA, PNA, shunts (PDA, PFO) 3. ph, PaCO 2, PaO 2, electrolytes (Ca ++ i) 3. Pathology: cytokines, chemokines Non-vital organ blood flow distribution Soleymani et al, J Perinatol 21; 3:S38-S45 Adequacy of blood flow is the goal but cannot be ensured by clinical exam (e.g. cap refill time) and laboratory test (e.g. lactate) Osborn DA et al. Arch Dis Child 24;89:F Miletin J et al. Eur J Pediatr. 29;168:89-13 de Boode WP. Early Hum. Dev. 21; 86: Vast majority of studies show an association between hypotension and brain injury/outcome What is the cause of poor outcome? Hypotension Treatment Hypotension+treatment Other (hypotension is a marker) 3

4 9/16/212 Indicators of Hypotension during first 24 hrs and Neurodevelopmental Outcome at 24 months in Preterm Infants < 28 GA (n=945) After adjusting for confounders, none of the indicators of hypotension were associated with: 1) an MDI <7 or a PDI <7 2) Indicators of white matter damage or cerebral palsy 1) Logan J W et al. Arch Dis Child 211; 96:F ) Logan J W et al. J Perinatol. 211; 31: Challenges in Assessing Effect of Hypotension on Outcome Common practice of treating hypotension Temporal relation to other factors affecting organ perfusion (e.g. PDA) Dysregulated inflammation Lack of definition of hypotension based on vital organ blood flow Lack of RCT evaluating the effect of hypotension and treatment on outcome Feasibility Study of Early Blood Pressure Management in Extremely Preterm Infants Of 48 not enrolled, 41 (85%) received treatment for hypotension Attending refused (n=13) In seven NICUs and among a population of 336 only 1 were studied in 1 year! Consent obtained in 17% of eligible infants. All neonates with pre-eligible consents (prenatal and postnatal) were not enrolled. Batton BJ et al. J Pediatr 212; 161:65-9 4

5 9/16/212 Factors Affecting the Potential Impact of Hypotension on Outcome Duration 1-3 Loss of autoregulation 4,5 Hypercarbia 6,7 Hypoxia 2 Metabolic acidosis 3 1. Hunt et al. J Pediatr. 24;145: Low JA et al. Acta Paediatr 1993;82: Goldstein RF et al. Pediatrics 1995;95: O Leary H. Pediatrics 29;124: Wong FY et al. PLoS one 212;7:e Kaiser et al, Pediatr Res 25; 58: Noori et al. APS-SPR 211 Hypotension (Mean BP < GA) and Neurodevelopmental Outcome at 3 years Average MBP % Readings MBP < GA Outcome First 12 h First 24 h First 12 h First 24 h Death and any disability.84 ( ).68 ( ) 1.25 ( ) 1.48 ( ) Death.98 ( ).49 (.26.93) 1.46 ( ) 1.47 ( ) Abnormal DQ.86 ( ).79 ( ) 1.15 ( ) 1.48 ( ) Abnormal motor 1.18 ( ) 1.1 ( ).98 ( ) 1.17 ( ) *OR (95% CI) adjusted for gestation, use of postnatal steroids, and level of maternal education n=126 Hunt et al. J Pediatr. 24;145: Case 1 A set of twin were born at 26 3/7 week via c-sec with no premature rupture of membrane. Apgar scores were 7 1 and 8 5. Both received surfactant and were put on conventional mechanical ventilation. Blood pressure and capillary refill were normal in the first week. 5

6 PaCO 2 (mmhg) (%) (cm/s) (%) (cm/s) MCA-MV (cm/s) 9/16/212 rso2 SPO2 Extraction MCA mean velocity * * * * * (hours) Twin A HUS: Normal Normal Normal Normal Normal Normal Normal 1 rso2 SPO2 Extraction * * * * * (hours) Twin B HUS: Normal Normal Normal G1 IVH G4 IVH 9 Twin A Twin B Hours After Birth Relationship between Middle Cerebral Artery Mean Velocity (MCA-MV) and PaCO 2 (First 3 Days after Birth, GA 25.9 ± 1.4 wks, hemodynamically stable) PaCO 2 (mmhg) n= 78 data pairs in 21 subjects Positive linear relationship between PaCO 2 and MCA-MV (R 2 =.3, p<.1). Noori et al. APS-SPR 211 (unpublished) 6

7 MCA-MV (cm/s) MCA-MV (cm/s) MCA-MV (cm/s) 9/16/212 Relationship between MCA-MV and PaCO 2 in First 3 Postnatal Days 45 R 2 =.49, p < PaCO 2 (mmhg) n= 78 data pairs in 21 subjects Using piece-wise bilinear regression models, a breakpoint was identified at mmhg of PaCO 2. Significant increase in CBF with CO 2 above low 5 s Noori et al. APS-SPR 211 (unpublished) Effect of Hypercapnia on Cerebral Blood Flow Autoregulation in 43 Ventilated VLBW Neonates Slope of autoregulatory plateau CBF-MABP relationship in the neonate A slope of near or equal to suggest intact cerebral autoregulation CBF autoregulation is affected by PaCO 2 Kaiser et al, Pediatr Res 25; 58:931 CBF and BP relationship adjusted for CO 2 level 7 6 PaCO 2 < 51 mmhg R 2 =.7 P = PaCO 2 51 mmhg R 2 =.133 P = MBP (mmhg) MBP (mmhg) MCA-MV had positive linear relationship with BP when adjusted for CO 2 No relationship when CO 2 < 51 mmhg A trend for positive linear relationship when CO 2 51 mmhg Attenuation of CBF autoregulation with high CO 2 Noori et al. APS-SPR 211 (unpublished) 7

8 9/16/212 Hypotension in Extremely Preterm Infants: Summary Hypotension is associated with poor outcome Adequacy of organ blood flow is the most important parameter but cannot be verified by clinical exam and laboratory tests Hypotension should be considered as one of the screening tool for adequacy of CV function Duration of hypotension, impairment of autoregulation and presence of co-existing derangements (hypoxemia, extremes of CO 2, hspda, metabolic acidosis) may augment the adverse effect of hypotension Principles of CVS Supportive Care Target the underlying pathophysiology Choose the right medication Titrate the medication to the desired effect Take into account the developmentally regulated differences in CVS in neonates versus older children Consider down-regulation of adrenergic receptors Beware of overshooting Pathophysiology of Shock Blood Pressure Cardiac output x Systemic Vascular Resistance Heart Rate x Stroke Volume Neuroendocrine and paracrin regulatory mechanisms Arrhythmia Preload Contractility Afterload Vasodilation Vasoconstriction Hypovolemia Diastolic dysfunction Volume overload Poor contractility Hyperdynamic myocardium High afterload Low afterload 8

9 CBF (ml/1g/min) 9/16/212 Selecting the right medication: Cardiovascular actions of adrenergic receptors Adrenergic, Dopaminergic and Vasopressin Receptors α 1 / α 2 β 2 α 1 β 1 / β 2 DA 1 / DA 2 V 1a Vascular Vascular Cardiac Cardiac Vascular/Cardiac Vascular Vasoconstriction Vasodilation * + Inotropy ++ +/++ + Chronotropy Cond. Velocity * = renal, mesenteric, coronary circulation > pulmonary circulation > extracranial vessels of the neck Noori & Seri. Clin Perinatol 212; 39: Selecting the right medication: Mechanisms of action of vasopressors, inotropes, and lusitropes Adrenergic, Dopaminergic and Vasopressin Receptors α 1 / α 2 β 2 α 1 β 1 / β 2 DA 1 / DA 2 V 1a Vascular Vascular Cardiac Cardiac Vascular/Cardiac Vascular Phenylephrine + Norepinephrine /+ ++ Epinephrine Dopamine Dobutamine +/ Isoprenaline Vasopressin PDE-III Inhibitors PDE-V Inhibitors Noori & Seri. Clin Perinatol 212; 39: Avoid Excessive increase in BP Control Pre-Dopamine Dopamine Mean BP (mmhg) n=17 preterm infants Mean BP (mmhg) CBF may be low in hypotensive preterm infants Once on vasopressor (e.g. dopamine), CBF improves BUT because of presence of a direct correlation with blood pressure (loss of autoregulation) reperfusion brain injury? Munro MJ. et al. Pediatrics 24;114:1591 9

10 9/16/212 Pathophysiology of Shock Blood Pressure Cardiac output x Systemic Vascular Resistance Heart Rate x Stroke Volume Neuroendocrine and paracrin regulatory mechanisms Arrhythmia Preload Contractility Afterload Vasodilation Vasoconstriction Hypovolemia Diastolic dysfunction Volume overload Poor contractility Hyperdynamic myocardium High afterload Low afterload Vasodilation - Septic shock - Systemic inflammatory disease, (e.g. NEC) - Pressor-resistant hypotension Cardiovascular Compromise Preterm Infants with Sepsis Have High Cardiac Output and Low SVR * * n=2 (5 died), GA 27 (25-32) weeks, clinical sepsis or NEC, 15 had positive blood culture No change in flow and mild increase in SVR among survivors Non-survivor had a significant drop in cardiac output and a sharp rise in SVR de Waal K, Evans N. J Pediatr 21;156:

11 9/16/212 SVRI And Cardiac Index (CI) In 3 Children with Fluid-resistant Septic Shock Central venous catheter-related Community acquired High CI > 5.5 Hemodynamic response may vary depending on the bacteria Septic shock in late stages may be associated with myocardial dysfunction Brierley J. et al. Pediatrics 28;122: Vasodilatory Shock Treatment Volume Vasopressor (e.g. dopamine, epinephrine) Corticosteroid as a second line *Significant hemodynamic variability among preterm infants who survive 1 1. de Waal K et al. J Pediatr 21 Vasodilation - Septic shock - Systemic inflammatory disease, (e.g. NEC) - Pressor-resistant hypotension Poor Contractility - Asphyxia - Perinatal depression - Septic shock (late stage) - Dilated cardiomyopathy - LV non-compaction - Maladaptation after birth Cardiovascular Compromise 11

12 9/16/212 Case #2 A preterm infant was born at 24 1/7 week (BW 85g) via vaginal delivery after prolonged rupture of membrane without signs of chorioamnionitis. Apgar scores were 2 1, 1 5, 2 1 and the baby required a brief chest compression. Initial ABG 7.5/92/12/-5/25 on SIMV FiO Switched to HFO with normal blood gases afterward. At 12 hrs ABG 7.33/37/47/-6/2 - BP 31/25 28 CRT <2 sec - Hct 47 septum LV post Wall SF 22% SF 37% RVO (ml/k/min) 49 RVO (ml/k/min) 228 Short axis view (LV) M-mode (LV) Pulm. Doppler A 4 hours old 25 6/7 wk preterm infants with severe myocardial dysfunction, low systemic and cerebral blood flow due placental abruption. Patients responds to dobutamine. Pulm. Artery (systemic flow) Middle Cerebral Artery Dobutamine started Dobutamine started 12

13 SMA SV (cm/s) Cardiac Output (ml/k/min) Renal a. SV (cm/s) A. Cerebral a. SV (cm/s) 9/16/212 Cardiovascular Impact of Dobutamine in Neonates with Myocardial Dysfunction * * Pre Dob 2 min Dob 8-1h Pre Dob 2 min Dob 8-1h * * Pre Dob 2 min Dob 8-1h Pre Dob 2 min Dob 8-1h n=2, GA wk, postnatal age days, dobutamine mcg/k/min Robel-Tillig et al. Early Hum Dev. 27;83:37 Asphyxia/Perinatal Depression Cause of circulatory compromise myocardial dysfunction (± compensatory vasoconstriction) Treatment inotropes e.g. dobutamine avoid excessive fluid boluses Vasodilation - Septic shock - Systemic inflammatory disease, (e.g. NEC) - Pressor-resistant hypotension High Afterload - Maladaptation after birth - Dilated cardiomyopathy Poor Contractility - Asphyxia - Perinatal depression - Septic shock (late stage) - Dilated cardiomyopathy - LV non-compaction - Maladaptation after birth Cardiovascular Compromise 13

14 Contractility 9/16/212 Sensitivity of Immature Myocardium to Afterload Afterload Adapted from Rowland & Gutgesell, Am J Cardiol 1995 Treatment Inotrope (e.g. dobutamine)? Lucitrope (e.g. milrinone)? Vasodilation - Septic shock - Systemic inflammatory disease, (e.g. NEC) - Pressor-resistant hypotension High Afterload - Maladaptation after birth - Dilated cardiomyopathy Hypovolemia - Acute blood loss - Umbilical cord avulsion - Subgaleal hemorrhage - insensible water loss - Polyuria Poor Contractility - Asphyxia - Perinatal depression - Septic shock (late stage) - Dilated cardiomyopathy - LV non-compaction - Maladaptation after birth Cardiovascular Compromise 14

15 9/16/212 Hemodynamic Effects of Delayed Cord Clamping in Premature Infants RCT, n=41, mean GA ~28 weeks, DCC=45 s, ICC= 5 s Higher SVC flow in delayed cord clamping group Higher RVO in delayed cord clamping group only at 48 hours No difference in MCA or SMA flow velocity, shortening fraction Sommers et al. Pediatrics. 212; 129:e Post Abdominal Surgery 1 month old former 23 week premie with NEC and perforation. Post-operative: Received multiple fluid boluses and escalating dose of dopamine up to 25 mcg/kg/min for persistent hypotension & metabolic acidosis BP 26/17 21 Base excess Echo SF 48% LVO 243 ml/kg/min Case #3 Vasodilation - Septic shock - Systemic inflammatory disease, (e.g. NEC) - Pressor-resistant hypotension High Afterload - Maladaptation after birth - Dilated cardiomyopathy Hypovolemia - Acute blood loss - Umbilical cord avulsion - Subgaleal hemorrhage - insensible water loss - Polyuria Poor Contractility - Asphyxia - Perinatal depression - Septic shock (late stage) - Dilated cardiomyopathy - LV non-compaction - Maladaptation after birth Cardiovascular Compromise Diastolic Dysfunction - Tension pneumothorax - Cardiac tamponade - Hypertrophic cardiomyopathy (e.g. IDM) 15

16 9/16/212 Case #4 A 5.4 kg term infant, born to an insulin-dependent diabetic mother, presents with hypotension and moderate metabolic acidosis 2 hours after birth. Echocardiogram shows significant myocardial hypertrophy, dynamic left ventricular outflow tract obstruction, a closing PDA with bidirectional shunting and otherwise normal cardiac anatomy. Echocardiogram: M-mode LV Septum Post Wall LV Normal IDM with HCM Hypertrophic Cardiomyopathy Cause of circulatory failure diastolic dysfunction low preload hyperdynamic myocardium dynamic LV outflow obstruction Treatment VOLUME Beta-blocker (esmolol drip) Vasopressor AVOID inotropes Vasodilation - Septic shock - Systemic inflammatory disease, (e.g. NEC) - Pressor-resistant hypotension High Afterload - Maladaptation after birth - Dilated cardiomyopathy Hypovolemia - Acute blood loss - Umbilical cord avulsion - Subgaleal hemorrhage - insensible water loss - Polyuria Poor Contractility - Asphyxia - Perinatal depression - Septic shock (late stage) - Dilated cardiomyopathy - LV non-compaction - Maladaptation after birth Cardiovascular Compromise - PDA Shunt - AV malformation Diastolic Dysfunction - Tension pneumothorax - Cardiac tamponade - Hypertrophic cardiomyopathy (e.g. IDM) 16

17 % change MAP (mmhg) 9/16/212 Case # 5 A preterm infant (twin A) was born at 31 1/7 weeks gestation (BW 118g, 8%ile) via c-sec due to abnormal cord Doppler study. No signs of chorioamnionitis. Apgar scores were 4 1 and 7 5. The baby is on no respiratory support and blood gases are normal. However, the baby has been hypotensive despite receiving a bolus of NS. Now at 3 hours after birth, blood pressure is 34/14 (21) and capillary refill is 2-3 sec. With regard to hemodynamic status, what would be the best course of action: 1) No intervention; continue close monitoring 2) Give another 1-2 ml/kg.9 NS bolus 3) Start dobutamine at 5 mcg/kg/min and titrate 4) Start dopamine at 5 mcg/kg/min and titrate 5) Start epinephrine at.5 mcg/kg/min and titrate Short axis view (LV) Aorta Doppler LVO = 377 ml/k/min M-mode (LV) Middle Cerebral Artery Doppler SF 34% MV 23 cm/s hr 9hr 33hr LVO SVR MAP hr 9hr 33hr 17

18 9/16/212 Not all hypotensive infant need treatment if adequacy of organ blood flow can be verified Objective Assessment of Hemodynamics Beyond BP Functional echocardiography Non-invasive continuous cardiac output monitor Tissue oxygen saturation Near infra-red spectroscopy Visible light spectroscopy Continuous Cardiac Output Monitor Based on Electrical Cardiometry (Thoracic Electrical Biompedance) Aorta prior to Aortic Valve Opening Aorta after Aortic Valve Opening No Flow Random Orientation Pulsatile Flow Alignment Non-invasive Simple to use Need to be further validated Aesculon 18

19 LVO (ml/min) (ml/min) 9/16/212 Continuous Non-Invasive Cardiac Output Measurements in the Neonate by Electrical Cardiometry: A Comparison with Echocardiography ᴏ ᴏ Electrical Cardiometry Echo 115 paired measurements in 2 healthy term neonates in first 2 days Noori et al. Arch Dis Child 212; 97:F34-3 Agreement between Left Ventricle Output Estimated by Echocardiography and Electrical Cardiometry. 115 paired measurements in 2 healthy term neonates in first 2 days True precision = 31% which is considered clinically acceptable Noori et al. Arch Dis Child 212; 97:F34-3 Non-invasive Cardiac Output Monitoring In Neonates Using Bioreactance: A Comparison With Echocardiography 97 paired measurements in 1 neonates weeks gestation Bias 153 ± 56 ml/min Limit of agreement = 43, 267 ml/min NICOM consistently under-read LVO by 31 ± 8.8% (Limit of agreement = 15%, 46%) Weisz et alneonatology. 212; 12:

20 9/16/212 Tissue Oxygen Saturation: Near Infra-Red Spectroscopy INVOS INVOS Fore-Sight Tissue Oxygen Saturation: Visible Light Spectroscopy (T-Stat, SPECTROS) Buccal tissue saturation is 61 to 72% in normal term neonates Correlates with LVO May be useful in detecting early stage of shock Noori et al. J Perinatol 211 Level of Monitoring BP or clinical assessment of flow BP + clinical assessment of flow + pathophysiology Identify possible underlying pathophysiology based on the history + Echocardiography Identify underlying pathophysiology + Organ blood flow Ensuring adequate organ blood flow and function 2