Gazi University Faculty of Medicine Department of Anesthesiology OBSTETRIC PAIN AND ITS MANAGEMENT IN THE PERINATAL PERIOD : WHAT DO WE NEED TO KNOW? Teşekkür+Bu konudaki bilgileri sizlerle paylaşmak istiyorum. Berrin Günaydın, MD, PhD Gazi University Faculty of Medicine Department of Anesthesiology ANKARA, TURKEY

Pain relief methods for labor and delivery Non-pharmacological Simple analgesic techniques Complementary & alternative therapies Pharmacological Inhalation analgesia (volatile and N2O) Systemic analgesia Neuraxial analgesia There are various …….as non-pharmacological or pharmacological

Epidural/CSE Analgesia Atraumatic vaginal breech delivery Vaginal delivery of twin infants and preterm infant Does not prolong the 1st stage of labor and the rate of C/S Blood pressure control in preeclamptic women Epidural/CSE Analgesia Does increase the duration of 2nd stage of labor and the rate of instrumental delivery Neuraxial analgesia either by epidural or CSE may offer many advantages over other techniques by providing better analgesia. For instance; epidural analgesia may facilitate….By effective pain relief, it facilitates… According to the systematic and independent results of 3 metanalysis, neuraxial analgesia does prolong the 2nd stage of labor (approxiamately 24 min) and the rate of intstruemental delivery Blunts hemodynamic effects of uterine contractions (sudden increase in preload) the associated pain response in patients with medical complications (mitral stenosis, spinal cord injury, intracranial neurovascular disease, asthma)

Preparation for Neuraxial Analgesia Indications “in the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labor” Contraindications Patient refusal or inability to cooperate Increased intracranial pressure secondary to a mass lesion Skin or soft tissue infection at the needle placement Frank coagulability Uncorrected maternal hypovolemia Inadequate training or experience with the technique In 2006 ACOG and in 2007 ASA reaffirmed the earlier jointly published opinion statement that…….

Neuraxial Analgesia Preanesthetic evaluation Timing of neuraxial analgesia Neuraxial analgesia induction Epidural or Combined Sinal Epidural (CSE) Neuraxial analgesia maintenance (PCEA) Background infusion and/or bolus on demand *Ginseng, Garlic, Gingko Kuczkowski . Arch Obstet Gynecol 2006 History* (anesthetic/obstetric) Physical exam (vital signs, baseline blood pressure, airway, heart , lungs & back) Platelet count, blood type-cross match Obstetric Anesthesia Practice Guidelines 2007 Thorough preparation of neuraxial analgesia involves several steps.

Timing of Neuraxial Analgesia Neuraxial analgesia in early labor (defined as regular uterine contractions that cause progressive effacement and dilation of the uterine cervix) did not increase rate of C/S provided better analgesia resulted in a shorter duration of labor than systemic analgesia According to the Obstetric Anesthesia Practice Guidelines 2007

Timing of Neuraxial Analgesia Genellikle aktif eylemde düzenli kontraksiyon ve serviks dilatasyonu >3 cm

Types of Neuraxial Analgesia Continuous (Epidural, CSE, Spinal & Caudal) Single-shot spinal Technique Advantages Disadvantages Epidural Continuous analgesia No dural puncture required Ability to extend analgesia to anesthesia for C/S -Slow onset of analgesia -Larger drug dose requirement -Greater risk of maternal systemic toxicity -Greater fetal drug exposure CSE Low dose local anesthetic & opioid Rapid onset analgesia Rapid onset sacral analgesia Complete analgesia with opioid alone Decreased incidence of failed epidural analgesia -Delayed verification of functioning epidural catheter -Higher incidence of pruritis -Possible higher risk of fetal bradycardia

NEURAXIAL ANALGESIA FOR LABOR EPIDURAL CSE Local anesthetics and/or opioids Chestnut’s Obstetric Anesthesia Principals and Practice 2009

Choice of Amide Local Anesthetics for Neuraxial Analgesia Bupivacaine 96% protein bound F/M: 0.2-0.4 (UV/MV:0.3) Ropivacaine 92 (90-95)% protein bound, F/M: 0.2 40% less potent than bupivacaine Levobupivacaine 97% protein bound, 0.98 as potent as bupivacaine There are advantages and disadvantages for each technique which are...

INITIATION OF NEURAXIAL ANALGESIA FOR LABOR EPIDURAL CSE 2% Chloroprocaine Effective analgesia for 40 min Commonly used for extension of epidural labor analgesia for instrumental delivery or emergency C/S Lidocaine Test dose: 1.5% with 5 µg/mL epinephrine Choice of Local Anesthetics (5-20 mL) Bupivacaine 0.0625%-0.125% Ropivacaine 0.08%-0.2% Levobupivacaine 0.0625%-0.125% Choice of Opioids (lipid soluble) Fentanil 50-100 µg Sufentanil 5-10 µg The volume required to initiate epidural labor analgesia is 5-20 mL of local anesthetic solution. The local anesthetic dose/concentration and the fentanyl or sufentanyl dose are reduced if the drugs are combined or if a local anesthetic containing epidural test dose is administered before the initial therapeutic dose. Chestnut’s Obstetric Anesthesia Principals and Practice 2009

INITIATION OF NEURAXIAL ANALGESIA FOR LABOR EPIDURAL CSE Choice of Opioids Fentanyl F/M: 0.37-0.57 Lipid solubility:816 Intrathecal ED50: 14-18 µg ED95: 20-30 µg Sufentanil F/M: 0.81 Lipid solubility:1727 Intrathecal ED50: 2-4 µg ED95: 9-15 µg When opioids used alone… Chestnut’s Obstetric Anesthesia Principals and Practice 2009

Intrathecal ED95 of Local Anesthetics with Opioids INITIATION OF NEURAXIAL ANALGESIA FOR LABOR EPIDURAL CSE Intrathecal ED95 of Local Anesthetics with Opioids Sufentanil 1.5 µg ED95 Bupivacaine 3.3 mg ED95 Ropivacaine 4.8 mg ED95 Levobupivacaine 5 mg Van de Velde et al. Anesthesiology 2007 When opioids used alone… Fentanyl 15 µg ED95 Bupivacaine: 1.66 mg (1.75 mg) Whitty et al. IJOA 2007

Epidural adjuvants (neostigmine & clonidine) INITIATION OF NEURAXIAL ANALGESIA FOR LABOR EPIDURAL CSE Epidural adjuvants (neostigmine & clonidine) Intrathecal labor analgesia by ropivacaine & sufentanil Followed by 10 mL of epidural neostigmine 500 µg + clonidine 75 µg vs placebo Prolonged analgesia Reduced ropivacaine consumption/hour via PCEA More parturients delivered before 1st additional dose When opioids used alone… Van de Velde IJOA 2009

MAINTENANCE OF NEURAXIAL LABOR ANALGESIA PCEA Concentration of Local Anesthetics Bupivacaine 0.05%-0.125% Ropivacaine 0.08%-0.2% Levobupivacaine 0.0625%-0.125% Concentration of Opioids Fentanyl 2 (1.5-3) µg/mL Sufentanil 0.2-0.33 µg/mL When opioids used alone… Chestnut’s Obstetric Anesthesia Principals and Practice 2009

PCEA Basal Infusion Only Bolus (on demand) + Bolus (on demand) 0.0625%, 0.08%, 0.1%, 0.125% bupivacaine + 2 µg/mL fentanyl 5 , 8, 10, 12, 15 mL/h Labor analgesia initiated by either intrathecal 20 µg fentanyl or epidural bupivacaine 0.1% including 50 µg fentanyl (7 mL) followed by 0.1% bupivacaine+2 µg/mL fentanyl 5 mL bolus 10 min lock-out Sezer & Gunaydin. IJOA 2007 0.0625%, 0.08%, 0.1%, 0.125 % bupivacaine + 2 µg/mL fentanyl 5 -15 mL/hr 5 mL bolus 10 -15 min lock-out 25 -30 mL/h limit

Basal Infusion+Bolus (on demand) PCEA Basal Infusion Only Bolus (on demand) Basal Infusion+Bolus (on demand) Labor analgesia was initiated by Intrathecal bupivacaine 2.5 mg+fentanyl 25 µg Followed by PCEA protocol (5 mL demand, 10 min lock-out with or without background infusion of 6 mL/h, 30 mL/h limit) containing epidural solution (ropivacaine 0.1% with fentanyl 2 µg/mL) Reduced PCEA demanding dose But not total amount of ropivacaine and fentanyl/hour Okutomi et al. IJOA 2009

Basal Infusion+Bolus (on demand) PCEA Basal Infusion Only Bolus (on demand) Basal Infusion+Bolus (on demand) Labor analgesia was initiated by Intrathecal ropivacaine 2 mg+fentanil 15 µg Followed by PCEA protocol (ropivacaine 0.1% with fentanyl 2 µg/mL) 5 mL demand only, 15 min lock-out 5 mL demand on bolus, 12 min lock-out with 5 mL/h infusion 5 mL demand on bolus, 10 min lock-out with 10 mL/h infusion 5 mL demand only PCEA resulted less local anesthetic consumption with higher incidence of breakthrough pain and pain scores than others Lim et al. Anesth Analg 2008

Timing of PCEA Labor analgesia was initiated by Intrathecal bupivacaine 2.5 mg+fentanyl 25 µg PCEA (5 mL demand, 10 min lock-out with background infusion of 10 mL/h, 30 mL/h limit) containing epidural solution (ropivacaine 0.1% with fentanyl 2 µg/mL& 1:500 000 epinephrine) was initiated 3, 30, 60 and 90 minutes Best timing of epidural infusion was within 30 min after intrathecal labor analgesia induction Okutomi et al. IJOA 2008

After initiation of neuraxial analgesia Side Effects Pruritis, shivering, urinary retention, delayed gastric emptying, maternal fever, fetal heart rate changes After initiation of neuraxial analgesia Intense pain relief Sudden decraese in epinephrine levels When opioids used alone… Unchanged norepinephrine levels Uterine hypertonicity (Tachysystole) fetal bradycardia

Conclusion Choice of a specific neuraxial technique should be individualized based on the anesthetic and obstetric risk factors, patient preferences, progress of labor and resources of the facility Regardless of the technique, primary goal is to provide adeaquate maternal analgesia preferably with minimal motor block which can be achieved by low concentrations of local anesthetics commonly with opioids.

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Gazi University School of Medicine Department of Anaesthesiology NEURAXIAL ANALGESIA FOR LABOR: STANDARD TECHNIQUES VERSUS NOVEL APPROACH Selin Erel, MD Gazi University School of Medicine Department of Anaesthesiology Ankara, Turkey

Outline Labor Analgesia Methods Types of Neuraxial Labor Analgesia Comparative Effects of Neuraxial Techniques Onset of analgesia Spread of analgesia Catheter adjustment Block quality Physician top up requirement Maternal side effects & complications Uterine contractions Fetal outcomes Progress of labor Mode of delivery Neonatal outcomes How to Perform DPE Technique

Labor analgesia methods Non-pharmacological Simple analgesic techniques Complementary & alternative therapies Pharmacological Inhalation analgesia (volatile and N2O) Systemic analgesia Neuraxial analgesia There are various …….as non-pharmacological or pharmacological

(Epidural/CSE) Analgesia Atraumatic vaginal breech delivery Vaginal delivery of twin infants and preterm infant Does not prolong the 1st stage of labor and the rate of C/S Blood pressure control in preeclamptic women Neuraxial (Epidural/CSE) Analgesia Does increase the duration of 2nd stage of labor and the rate of instrumental delivery Neuraxial analgesia either by epidural or CSE may offer many advantages over other techniques by providing better analgesia. For instance; epidural analgesia may facilitate….By effective pain relief, it facilitates… According to the systematic and independent results of 3 metanalysis, neuraxial analgesia does prolong the 2nd stage of labor (approxiamately 24 min) and the rate of intstruemental delivery Blunts hemodynamic effects of uterine contractions (sudden increase in preload) the associated pain response in patients with medical complications (mitral stenosis, spinal cord injury, intracranial neurovascular disease, asthma)

Preparation for Neuraxial Analgesia Indications “in the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labor” Contraindications Patient refusal or inability to cooperate Increased intracranial pressure secondary to a mass lesion Skin or soft tissue infection at the needle placement Frank coagulability Uncorrected maternal hypovolemia Inadequate training or experience with the technique In 2006 ACOG and in 2007 ASA reaffirmed the earlier jointly published opinion statement that…….

Neuraxial Analgesia Preanesthetic evaluation Timing of neuraxial analgesia Neuraxial analgesia induction Epidural or Combined Sinal Epidural (CSE) Neuraxial analgesia maintenance (PCEA) Background infusion and/or bolus on demand *Ginseng, Garlic, Gingko Kuczkowski . Arch Obstet Gynecol 2006 History* (anesthetic/obstetric) Physical exam (vital signs, baseline blood pressure, airway, heart , lungs & back) Platelet count, blood type-cross match Obstetric Anesthesia Practice Guidelines 2007 Thorough preparation of neuraxial analgesia involves several steps.

Timing of Neuraxial Analgesia Neuraxial analgesia in early labor (defined as regular uterine contractions that cause progressive effacement and dilation of the uterine cervix) did not increase rate of C/S provided better analgesia resulted in a shorter duration of labor than systemic analgesia According to the Obstetric Anesthesia Practice Guidelines 2007

Timing of Neuraxial Analgesia Genellikle aktif eylemde düzenli kontraksiyon ve serviks dilatasyonu >3 cm

Types of Neuraxial Analgesia Continuous (Epidural, CSE, Spinal & Caudal) Single-shot spinal Technique Advantages Disadvantages Epidural Continuous analgesia No dural puncture required Ability to extend analgesia to anesthesia for C/S -Slow onset of analgesia -Larger drug dose requirement -Greater risk of maternal systemic toxicity -Greater fetal drug exposure CSE Low dose local anesthetic & opioid Rapid onset analgesia Rapid onset sacral analgesia Complete analgesia with opioid alone Decreased incidence of failed epidural analgesia -Delayed verification of functioning epidural catheter -Higher incidence of pruritis -Possible higher risk of fetal bradycardia

NEURAXIAL ANALGESIA FOR LABOR EPIDURAL CSE Local anesthetics and/or opioids Chestnut’s Obstetric Anesthesia Principals and Practice 2009

Choice of Amide Local Anesthetics for Neuraxial Analgesia Bupivacaine 96% protein bound F/M: 0.2-0.4 (UV/MV:0.3) Ropivacaine 92 (90-95)% protein bound, F/M: 0.2 40% less potent than bupivacaine Levobupivacaine 97% protein bound, 0.98 as potent as bupivacaine There are advantages and disadvantages for each technique which are...

INITIATION OF NEURAXIAL ANALGESIA FOR LABOR EPIDURAL CSE 2% Chloroprocaine Effective analgesia for 40 min Commonly used for extension of epidural labor analgesia for instrumental delivery or emergency C/S Lidocaine Test dose: 1.5% with 5 µg/mL epinephrine Choice of Local Anesthetics (5-20 mL) Bupivacaine 0.0625%-0.125% Ropivacaine 0.08%-0.2% Levobupivacaine 0.0625%-0.125% Choice of Opioids (lipid soluble) Fentanil 50-100 µg Sufentanil 5-10 µg The volume required to initiate epidural labor analgesia is 5-20 mL of local anesthetic solution. The local anesthetic dose/concentration and the fentanyl or sufentanyl dose are reduced if the drugs are combined or if a local anesthetic containing epidural test dose is administered before the initial therapeutic dose. Chestnut’s Obstetric Anesthesia Principals and Practice 2009

INITIATION OF NEURAXIAL ANALGESIA FOR LABOR EPIDURAL CSE Choice of Opioids Fentanyl F/M: 0.37-0.57 Lipid solubility:816 Intrathecal ED50: 14-18 µg ED95: 20-30 µg Sufentanil F/M: 0.81 Lipid solubility:1727 Intrathecal ED50: 2-4 µg ED95: 9-15 µg When opioids used alone… Chestnut’s Obstetric Anesthesia Principals and Practice 2009

Intrathecal ED95 of Local Anesthetics with Opioids INITIATION OF NEURAXIAL ANALGESIA FOR LABOR EPIDURAL CSE Intrathecal ED95 of Local Anesthetics with Opioids Sufentanil 1.5 µg ED95 Bupivacaine 3.3 mg ED95 Ropivacaine 4.8 mg ED95 Levobupivacaine 5 mg Van de Velde et al. Anesthesiology 2007 When opioids used alone… Fentanyl 15 µg ED95 Bupivacaine: 1.66 mg (1.75 mg) Whitty et al. IJOA 2007

Epidural adjuvants (neostigmine & clonidine) INITIATION OF NEURAXIAL ANALGESIA FOR LABOR EPIDURAL CSE Epidural adjuvants (neostigmine & clonidine) Intrathecal labor analgesia by ropivacaine & sufentanil Followed by 10 mL of epidural neostigmine 500 µg + clonidine 75 µg vs placebo Prolonged analgesia Reduced ropivacaine consumption/hour via PCEA More parturients delivered before 1st additional dose When opioids used alone… Van de Velde IJOA 2009

MAINTENANCE OF NEURAXIAL LABOR ANALGESIA PCEA Concentration of Local Anesthetics Bupivacaine 0.05%-0.125% Ropivacaine 0.08%-0.2% Levobupivacaine 0.0625%-0.125% Concentration of Opioids Fentanyl 2 (1.5-3) µg/mL Sufentanil 0.2-0.33 µg/mL When opioids used alone… Chestnut’s Obstetric Anesthesia Principals and Practice 2009

PCEA Basal Infusion Only Bolus (on demand) + Bolus (on demand) 0.0625%, 0.08%, 0.1%, 0.125% bupivacaine + 2 µg/mL fentanyl 5 , 8, 10, 12, 15 mL/h Labor analgesia initiated by either intrathecal 20 µg fentanyl or epidural bupivacaine 0.1% including 50 µg fentanyl (7 mL) followed by 0.1% bupivacaine+2 µg/mL fentanyl 5 mL bolus 10 min lock-out Sezer & Gunaydin. IJOA 2007 0.0625%, 0.08%, 0.1%, 0.125 % bupivacaine + 2 µg/mL fentanyl 5 -15 mL/hr 5 mL bolus 10 -15 min lock-out 25 -30 mL/h limit

Basal Infusion+Bolus (on demand) PCEA Basal Infusion Only Bolus (on demand) Basal Infusion+Bolus (on demand) Labor analgesia was initiated by Intrathecal bupivacaine 2.5 mg+fentanyl 25 µg Followed by PCEA protocol (5 mL demand, 10 min lock-out with or without background infusion of 6 mL/h, 30 mL/h limit) containing epidural solution (ropivacaine 0.1% with fentanyl 2 µg/mL) Reduced PCEA demanding dose But not total amount of ropivacaine and fentanyl/hour Okutomi et al. IJOA 2009

Basal Infusion+Bolus (on demand) PCEA Basal Infusion Only Bolus (on demand) Basal Infusion+Bolus (on demand) Labor analgesia was initiated by Intrathecal ropivacaine 2 mg+fentanil 15 µg Followed by PCEA protocol (ropivacaine 0.1% with fentanyl 2 µg/mL) 5 mL demand only, 15 min lock-out 5 mL demand on bolus, 12 min lock-out with 5 mL/h infusion 5 mL demand on bolus, 10 min lock-out with 10 mL/h infusion 5 mL demand only PCEA resulted less local anesthetic consumption with higher incidence of breakthrough pain and pain scores than others Lim et al. Anesth Analg 2008

Timing of PCEA Labor analgesia was initiated by Intrathecal bupivacaine 2.5 mg+fentanyl 25 µg PCEA (5 mL demand, 10 min lock-out with background infusion of 10 mL/h, 30 mL/h limit) containing epidural solution (ropivacaine 0.1% with fentanyl 2 µg/mL& 1:500 000 epinephrine) was initiated 3, 30, 60 and 90 minutes Best timing of epidural infusion was within 30 min after intrathecal labor analgesia induction Okutomi et al. IJOA 2008

After initiation of neuraxial analgesia Side Effects Pruritis, shivering, urinary retention, delayed gastric emptying, maternal fever, fetal heart rate changes After initiation of neuraxial analgesia Intense pain relief Sudden decraese in epinephrine levels When opioids used alone… Unchanged norepinephrine levels Uterine hypertonicity (Tachysystole) fetal bradycardia

Conclusion Choice of a specific neuraxial technique should be individualized based on the anesthetic and obstetric risk factors, patient preferences, progress of labor and resources of the facility Regardless of the technique, primary goal is to provide adeaquate maternal analgesia preferably with minimal motor block which can be achieved by low concentrations of local anesthetics commonly with opioids.

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Subarachnoid Epidural Subcutaneous space space duramater ligamentum flavum skin

Subarachnoid space Epidural space Subcutaneous duramater ligamentum flavum skin

Onset of analgesia Time to NPRS≤1 EPL DPE CSE p NPRS≤1 (min) 18 (10-120) 11 (4-120) 2 (0.5-6)* .0001 *P=0.0001 versus EPL and DPE Values are expressed as median (interquartile range)

Advantages Onset of analgesia is faster with CSE tahn EPL & DPE but EPL and DPE ara comparable Spread of sacral analgesia (at 20 min) with DPE is similar and they are both better than EPL Block quality…………….

Spread of Analgesia Bilateral block at T10 EPL CSE DPE 0.5 min 6 (15) 20 (50) 10 min 30 (75) 40 (100) 38 (95) 20 -30 min Bilateral block at S2 EPL CSE DPE 0.5 min 0 (0) 11 (27.5) 3 (3.75) 10 min 15 (37.5) 38 (95) 32 (80) 20 min 25 (62.5) 40 (100) 30 min 34 (85) No block 2 (5) Values are expressed as n (%)

Intervention Catheter EPL CSE DPE Adjustment 4 (10) 3 (7.5) 2 (5) Replacement 0 (0) Values are expressed as n (%)

Block Quality DPE ( vs EPL ) CSE (vs EPL ) DPE (vs CSE ) Bilateral block at S2 RR (95%CI) P OR 10 min 2.13 (1.39-3.28) <.001 2.53 (1.69-3.80) 0.84 (0.71-1.00) .043 20 min 1.60 (1.26-2.03) 1.00 (1.00-1.00) ∞ 30 min 1.18 (1.01-1.30) .034 (1.01-1.32)

Block Quality Asymmetrick block DPE ( vs EPL ) CSE (vs EPL ) DPE (vs CSE ) <30 min 0.70 (0.44-1.11) .12 0.35 (0.18-0.68) .001 2.00 (0.97-4.14) .051 >30 min 0.19 (0.07-0.51) <.001 1.00 (0.27-3.72) >.999 Physician top up 0.45 (0.23-0.86) .011 (0.65-1.55) Asymmetrick block DPE ( vs EPL ) CSE (vs EPL ) DPE (vs CSE ) <30 min 0.70 (0.44-1.11) .12 0.35 (0.18-0.68) .001 2.00 (0.97-4.14) .051 >30 min 0.19 (0.07-0.51) <.001 1.00 (0.27-3.72) >.999 Asymmetric Block EPL CSE DPE <30 min 23 (57.5) 8 (20)* 16 (40) >30 min 21 (52.5) 4 (10)*

Block Quality Asymmetrick block DPE ( vs EPL ) CSE (vs EPL ) DPE (vs CSE ) <30 min 0.70 (0.44-1.11) .12 0.35 (0.18-0.68) .001 2.00 (0.97-4.14) .051 >30 min 0.19 (0.07-0.51) <.001 1.00 (0.27-3.72) >.999 Asymmetric Block EPL CSE DPE <30 min 23 (57.5) 8 (20)# 16 (40) >30 min 21 (52.5) 4 (10)??? 4 (10) #P<0.001 versus EPL *P=0.0001 versus EPL and DPE????????????? Values are expressed as n (%)

Block Quality Asymmetric Block EPL CSE DPE <30 min 23 (57.5) 8 (20) 16 (40) >30 min 21 (52.5) 4 (10) Values are expressed as n (%) Asymmetrick block DPE (vs EPL) CSE ( vs EPL) DPE( vs CSE) <30 min 0.70 0.35 2.00 >30 min 0.19 1.00 Physician top up 0.45

Top Up Requirement EPL CSE DPE None 20 (50) 31 (77.5) 1≥Top Up 9 (22.5) Time to First Physician Top Up 270 (133) 132 (85) 250 (163)

Maternal Side Effects DPE ( vs EPL ) CSE (vs EPL ) DPE (vs CSE ) RR (95%CI) P OR Nausea 0.25 (0.03-2.14) 0.17 0.03-2.14 .17 1.00 0.06-15.44 >.999 Pruritus (0.27-3.72 6.75 2.60-17.53 <.001 0.15 0.06-0.38 Hypotension (0.31-3.19) 2.60 1.02-6.61 .032 0.38 0.15-0.98 Motor block 0.40 (0.15-1.03) .057 0.07-0.88 1.57 0.38-6.52 .53

Maternal Side Effects EPL CSE DPE Nausea 4 (10) 1 (2.5) Pruritus 27 (67.5) 4(10) Hypotension 5 (12.5) 13 (32.5) PDPH 0 (0) Values are expressed as n (%)

Maternal Complications EPL CSE DPE P values ?

Hypertonus or Tachysytol Uterine Contraction 1h before neuraxial analgesia Frequency (f) of contractions EPL CSE DPE Lowest 2.0 (1.3) 2.4 (1.1) 2.1 (1.1) Highest 3.8 (1.5) 4.2 (1.4) 3.9 (1.3) Hypertonus or Tachysytol EPL CSE DPE UH without bradycardia 7 (17.5) 3 (7.5) 2 (5) UH with bradycardia 0 (0) UT without bradycardia 1 (2.5) UT with bradycardia Total combined UT/UH 8 (20) 6 (15) Values are expressed as mean (SD) or n

Uterine Contraction 1h after neuraxial analgesia Frequency of contractions EPL CSE DPE Lowest 2.0 (1.0) 2.2 (1.0) 2.1 (1.1) Highest 3.9 (1.0) 4.6 (1.0) 4.1 (1.1) Hypertonus or Tachystol EPL CSE DPE UH without bradycardia 2 (5) 8 (20) UH with bradycardia 1 (2.5) 3 (7.5) 0 (0) UT without bradycardia 5 (12.5) UT with bradycardia Total Combined UT/UH 18 (45) 4 (10) Requirement for tocolysis 2 (5.0) Values are expressed as mean (SD) or n

Uterine Contractions DPE (vs EPL) CSE (vs EPL) DPE (vs CSE) Combined UT/UH RR (95% CI) P OR Baseline 1.00 (0.42-2.40) >.999 0.75 (0.29-1.97) .56 1.33 (0.51-3.49) Post neuraxial 0.80 (0.23-2.76) .72 3.60 (1.48-8.75) .001 0.22 (0.08-0.6) <.001

Fetal Outcomes FHR decelerations Early/Late/Variable (absent/minimal/moderate/marked) EPL CSE DPE Total (Before neuraxial block) 9 (22.5) 8 (20) 11 (27.5) Total (After neuraxial block) 17 (42.5) 21 (52.5) 18 (45.0) P>0.05 among the groups Values are expressed as n (%)

Progress of Labor EPL CSE DPE P values ?

Mode of Delivery EPL CSE DPE Vaginal 28 (70) 35 (87.5) 31 (77.5) Instrumental 1 (2.5) 3 (7.5) 5 (12.5) Cesaerean 11 (27.5) 2 (5) 4 (10) No emergency cesarean due to fetal deceleration Values are expressed as n (%)

Neonatal Outcomes Apgar <7 EPL CSE DPE 1 min 4 (10) 2 (5) 1 (2.5) 0 (0) Values are expressed as n (%)

How to Perform DPE

Comparative Effects of Neuraxial Techniques Onset of analgesia was presented as time to NPRS≤1 NPRS ≤1 EPL (n=40) CSE DPE at 0.5 min 1 (2.5) 14 (35) 6(15) at 10 min 16 (40) 35 (87.5) 20 (50) at 20 min 30 (75) 38 (95) 32 (80) at 30 min 31 (77.5) Values are expressed as n (%)