Epidural hyperthermia
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1 Epidural hyperthermia Obstetric Anaesthesia SIG meeting th May 2018 Sydney, Australia Dr Chris Mullington MB BS, PhD, FRCA
2 Biography
3 Contents Definition & history Incidence Maternal and neonatal consequences Mechanisms Clinical management
4 Contents Definition & history Incidence Maternal and neonatal consequences Mechanisms Clinical management
5 Definition Epidural for labour analgesia + Core temperature > 38 C
6 History Epidural group Epidural placement Pethidine group [Fusi, Lancet, 1989]
7 Incidence of hyperthermia (> 38 C) Study Design n Incidence (%) Odds ratio (95% CI) With epidural Without epidural p-value Douma, IJOA, 2015 RCT ( ) < Wassen, J Obstet Gynaecol, 2014 Observational ( ) < Greenwell, Pediatrics 2012 Observational < Riley, Obstet Gynecol, 2011 Observational ( ) < 0.01 de Orange, BJA, 2011 RCT Agakidis, J Matern Fetal Neonatal Med, 2011 Observational < Sharma, Anesthesiology, 2002 RCT < Yancey, Obstet Gynecol, 2001 Observational ( ) < 0.01 Lucas, AJOG, 2001 RCT ( ) < Kaul, A&A, 2001 Observational < Dashe, Obstet Gynecol, 1999 Observational Philip, Anesthesiology, 1999 RCT ( ) < Sharma, Anesthesiology, 1997 RCT < Mayer, Am J Perinatol, 1997 Observational < Lieberman, Pediatrics, 1997 Observational ( ) < Ramin, Obstet Gynecol, 1995 RCT < Ploeckinger, Gynecol Obstet, 1995 Observational < Herbst, Obstet Gynecol, 1995 Observational ( ) < Vinson, J Fam Prac, 1993 Observational [Adapted from Segal, A&A, 2010]
8 Incidence of hyperthermia (> 38 C) Study Design n Incidence (%) Odds ratio (95% CI) With epidural Without epidural p-value Douma, IJOA, 2015 RCT ( ) < Wassen, J Obstet Gynaecol, 2014 Observational ( ) < Greenwell, Pediatrics 2012 Observational < Riley, Obstet Gynecol, 2011 Observational ( ) < 0.01 de Orange, BJA, 2011 RCT Agakidis, J Matern Fetal Neonatal Med, 2011 Observational < Sharma, Anesthesiology, 2002 RCT < Yancey, Obstet Gynecol, 2001 Observational ( ) < 0.01 Lucas, AJOG, 2001 RCT ( ) < Kaul, A&A, 2001 Observational < Dashe, Obstet Gynecol, 1999 Observational Philip, Anesthesiology, 1999 RCT ( ) < Sharma, Anesthesiology, 1997 RCT < Mayer, Am J Perinatol, 1997 Observational < Lieberman, Pediatrics, 1997 Observational ( ) < Ramin, Obstet Gynecol, 1995 RCT < Ploeckinger, Gynecol Obstet, 1995 Observational < Herbst, Obstet Gynecol, 1995 Observational ( ) < Vinson, J Fam Prac, 1993 Observational [Adapted from Segal, A&A, 2010]
9 Adverse neonatal neurological outcomes 37.5 C C C > 38.3 C [Greenwell, Pediatrics, 2012]
10 Adverse neonatal neurological outcomes 37.5 C C C > 38.3 C [Greenwell, Pediatrics, 2012]
11 Adverse neonatal neurological outcomes 37.5 C C C > 38.3 C [Greenwell, Pediatrics, 2012]
12 Neonatal encephalopathy A clinically defined syndrome of disturbed neurological function in the earliest days of life in an infant born at or beyond 35 weeks of gestation, manifested by a subnormal level of consciousness or seizures, and often accompanied by difficulty with initiating and maintaining respiration and depression of tone and reflexes. [D Alton, Obstet Gynecol, 2014]
13 Neonatal sepsis evaluation and antibiotic therapy Sepsis evaluation Antibiotic therapy [Heesen, J Perinat, 2012]
14 Neonatal sepsis evaluation and antibiotic therapy Sepsis evaluation Antibiotic therapy [Heesen, J Perinat, 2012]
15 Maternal antibiotic therapy Group n (%) Epidural only (n = 97) 21 (22) Opioids only (n = 96) 6 (6) Epidural + Opioids (n = 94) 18 (19) [Mayer, Am J Perinatol, 1997]
16 Maternal antibiotic therapy Group n (%) Epidural only (n = 97) 21 (22) Opioids only (n = 96) 6 (6) Epidural + Opioids (n = 94) 18 (19) [Mayer, Am J Perinatol, 1997]
17 Operative delivery [Lieberman, Am J Public Health, 1999]
18 Potential mechanisms 1. Limitation of heat loss 2. Sterile inflammation
19 Potential mechanisms 1. Limitation of heat loss 2. Sterile inflammation
20 Sterile inflammation Fever Core temperature Time [Stitt, Fed Proc, 1979] [Netea, Clin Inf Dis, 2000]
21 Sterile inflammation Fever Core temperature Time [Stitt, Fed Proc, 1979] [Netea, Clin Inf Dis, 2000]
22 Sterile inflammation Fever Core temperature Time [Stitt, Fed Proc, 1979] [Netea, Clin Inf Dis, 2000]
23 Sterile inflammation Interleukin-6 [Goetzl, AJOG, 2002] [Riley, Obstet Gynecol, 2011]
24 Sterile inflammation - Methylprednisolone T C > 38 C Neonatal bacteraemia Placebo 22 (22%) 0 (0%) Low dose 17 (34%) 1 (2%) High dose 1 (2%) 4 (9%) [Goetzl, AJOG, 2006]
25 Sterile inflammation Infection? 1. Incidence of positive bacterial cultures Maternal With epidural (%) Without epidural (%) p-value Riley, Obstet Gynecol, Neonatal Wassen, Obstet Gynaecol, Agakidis, J Matern Fetal Neonat Med, Philip, Anesthesiology, Incidence of sepsis risk factors Eg. n vaginal examinations, duration of membrane rupture - No increased incidence associated with epidural analgesia [Riley, Obstet Gynecol, 2011; Sharma, Anesthesiology, 2002; Yancey, Obstet Gynecol, 2001; Mayer, Am J Perinatology, 1997]
26 Sterile inflammation Infection? 1. Incidence of positive bacterial cultures Maternal With epidural (%) Without epidural (%) p-value Riley, Obstet Gynecol, Neonatal Wassen, Obstet Gynaecol, Agakidis, J Matern Fetal Neonat Med, Philip, Anesthesiology, Incidence of sepsis risk factors Eg. n vaginal examinations, duration of membrane rupture - No increased incidence associated with epidural analgesia [Riley, Obstet Gynecol, 2011; Sharma, Anesthesiology, 2002; Yancey, Obstet Gynecol, 2001; Mayer, Am J Perinatology, 1997]
27 Sterile inflammation Infection? Cefotaxime Placebo [Sharma, A&A, 2014]
28 Sterile inflammation Infection? Cefotaxime Placebo [Sharma, A&A, 2014]
29 Sterile inflammation Two problems 1. Labour epidurals decrease O 2 consumption 2. Inflammation does not occur in other scenarios VO2 (ml kg -1 min -1 ) Before epidural After epidural Pethidine During contractions Between contractions 4.4 (0.6) 3.1 (0.4) * 2.7 (0.3) 2.5 (0.2) [Hagerdal, Anesthesiology, 1983] PCA Epidural [Beilin, A&A, 2003]
30 Sterile inflammation Two problems 1. Labour epidurals decrease O 2 consumption 2. Inflammation does not occur in other scenarios VO2 (ml kg -1 min -1 ) Before epidural After epidural Pethidine During contractions Between contractions 4.4 (0.6) 3.1 (0.4) * 2.7 (0.3) 2.5 (0.2) [Hagerdal, Anesthesiology, 1983] PCA Epidural [Beilin, A&A, 2003]
31 Sterile inflammation Two problems 1. Labour epidurals decrease O 2 consumption 2. Inflammation does not occur in other scenarios VO2 (ml kg -1 min -1 ) Before epidural After epidural Pethidine During contractions Between contractions 4.4 (0.6) 3.1 (0.4) * 2.7 (0.3) 2.5 (0.2) [Hagerdal, Anesthesiology, 1983] PCA Epidural [Beilin, A&A, 2003]
32 Sterile inflammation Two problems 1. Labour epidurals decrease O 2 consumption 2. Inflammation does not occur in other scenarios VO2 (ml kg -1 min -1 ) Before epidural After epidural Pethidine During contractions Between contractions 4.4 (0.6) 3.1 (0.4) * 2.7 (0.3) 2.5 (0.2) [Hagerdal, Anesthesiology, 1983] PCA Epidural [Beilin, A&A, 2003]
33 Limitation of heat loss Heat loss is regulated by: 1. Sweating 2. Cutaneous vasomotor tone a) Active vasoconstriction b) Active vasodilation Controlled by 2 components of the sympathetic nervous system: Noradrenergic pathway Cholinergic pathway [Kellogg, J appl physiol, 2006]
34 Limitation of heat loss Heat loss is regulated by: 1. Sweating 2. Cutaneous vasomotor tone a) Active vasoconstriction b) Active vasodilation Controlled by 2 components of the sympathetic nervous system: Noradrenergic pathway Cholinergic pathway [Kellogg, J appl physiol, 2006]
35 Limitation of heat loss Heat loss is regulated by: 1. Sweating 2. Cutaneous vasomotor tone a) Active vasoconstriction b) Active vasodilation Controlled by 2 components of the sympathetic nervous system: Noradrenergic pathway Cholinergic pathway [Kellogg, J appl physiol, 2006]
36 Limitation of heat loss Heat loss is regulated by: 1. Sweating 2. Cutaneous vasomotor tone a) Active vasoconstriction b) Active vasodilation Controlled by 2 components of the sympathetic nervous system: Noradrenergic pathway Cholinergic pathway Labour is a heat stress [Eliasson, Chest 1992]
37 Limitation of heat loss Heat loss is regulated by: 1. Sweating 2. Cutaneous vasomotor tone a) Active vasoconstriction b) Active vasodilation Controlled by 2 components of the sympathetic nervous system: Noradrenergic pathway Cholinergic pathway Labour is a heat stress During labour active vasodilation and sweating are required to prevent increasing body temperatures
38 Skin blood flow (% max cardiac output) Limitation of heat loss 60 Active vasodilation (ACh) No vasomotor tone 5 0 Cold Heat Active vasoconstriction (NA) Stress Stress Thermoneutral
39 Skin blood flow (% max cardiac output) Limitation of heat loss 60 Active vasodilation (ACh) 5 Elective CS No vasomotor tone 0 Cold Heat Active vasoconstriction (NA) Stress Stress Thermoneutral
40 Skin blood flow (% max cardiac output) Limitation of heat loss 60 Active vasodilation (ACh) Labour epidural? 5 Elective CS No vasomotor tone 0 Cold Heat Active vasoconstriction (NA) Stress Stress Thermoneutral
41 Blockade of active cutaneous vasodilation [Mullington, 2018]
42 Blockade of active cutaneous vasodilation [Mullington, 2018]
43 Blockade of active cutaneous vasodilation [Mullington, 2018]
44 Clinical management No evidence based interventions Paracetamol [Goetzl, AJOG, 2002] Steroids [Goetzl, AJOG, 2006] Prophylactic antibiotics [Sharma, A&A, 2014] Some food for thought Labour room temperature Consent Sepsis evaluation and treatment
45 Clinical management No evidence based interventions Paracetamol [Goetzl, AJOG, 2002] Steroids [Goetzl, AJOG, 2006] Prophylactic antibiotics [Sharma, A&A, 2014] Some food for thought Labour room temperature Consent Sepsis evaluation and treatment
46 Clinical management No evidence based interventions Paracetamol [Goetzl, AJOG, 2002] Steroids [Goetzl, AJOG, 2006] Prophylactic antibiotics [Sharma, A&A, 2014] Some food for thought Labour room temperature Consent Sepsis evaluation and treatment
47 Clinical management No evidence based interventions Paracetamol [Goetzl, AJOG, 2002] Steroids [Goetzl, AJOG, 2006] Prophylactic antibiotics [Sharma, A&A, 2014] Some food for thought Labour room temperature Consent Sepsis evaluation and treatment
48 Clinical management No evidence based interventions Paracetamol [Goetzl, AJOG, 2002] Steroids [Goetzl, AJOG, 2006] Prophylactic antibiotics [Sharma, A&A, 2014] Some food for thought Labour room temperature Consent Sepsis evaluation and treatment
49 Summary Epidural hyperthermia is common It has adverse maternal and neonatal consequences The underlying mechanism is unclear Currently there are no effective treatments
50
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