• labor pain is one of the most intense pains that awoman can experience, and it is typically worsethan a pain associated with a deep laceration.• 60% of primiparous women described the painof uterine contractions as being “unbearable,intolerable, extremely severe, or excruciating.”
Comparison of pain scores using theMcGill Pain Questionnaire
Mechanism of Labor PainFirst Stage of LaborPain Pathway in first stageParturients describe this pain as dull in nature and often poorly localized.
Mechanism of Labor Pain: Second Stage• Activation of the same afferents activatedduring the first stage of labor plus afferents thatinnervate the vaginal surface of the cervix, thevagina, and the perineum.• Afferents course through the pudendal nervewith DRG at S2-S4, and they are somatic innature.
Pain in labor – location and neural pathwaysSite of Origin Cause Pathway Site of PainUterus and cervix Contraction and distensionof uterus and dilatation ofcervixAfférent T10 – L1Post. Rami T10 – L1Upper abdomen togroin, mid back andinner upper thighs(referred pain)Peri-uterinetissue (mainlyposterior)Pressure often associatedwith occipito posteriorposition and flat sacrumLumbo sacral plexusL5- S1Mid and lower backand back of thighs(referred pain)Lower birth canal Distension of vagina andperineum in second stageSomatic roots S2- S4 Vulva, Vagina andPerineumBladder Over distension Sympathetic T11-L2Parasympathetic S2-S4Usually suprapubicMyometrium anduterine visceralperitoniumAbruptionScar dehiscenceT10-L1 Referred Pain to siteof pathology
Effects of labor pain on mother• Obstetric Course• Neural stimulation through pain pathways results inthe release of substances that either drive (oxytocin)or brake (epinephrine) uterine activity and cervicaldilation;• effect of analgesia on the course of labor can varybetween individuals.
• Cardiac and Respiratory Effects• The intermittent pain of uterine contractions alsostimulates respiration and results in periods ofintermittent hyperventilation. In the absence ofsupplemental oxygen administration, compensatoryperiods of hypoventilation between contractions resultin transient periods of maternal hypoxemia and, insome cases, fetal hypoxemia.
• Psychological Effects• Small proportion of women can be psychologicallyharmed by either providing or withholdinganalgesia• Both individual and environmental influences uponthis meaning.
Effects of labor pain on fetus• Labor pain affects multiple systems thatdetermine utero-placental perfusion:• (1) uterine contraction frequency and intensity, bythe effect of pain on the release of oxytocin andepinephrine;• (2) uterine artery vasoconstriction, by the effect ofpain on the release of norepinephrine andepinephrine; and• (3) maternal oxyhemoglobin desaturation, which mayresult from intermittent hyperventilation followed byhypoventilation
Child birth preparation:Psychoprophylaxis• “Natural childbirth” stems from a phrase coined byGrantley Dick-Read in 1933.• This method focuses on teaching the motherconditioned reflexes to overcome the pain and fearof childbirth.• It uses an education program, human support duringlabor, breathing techniques, relaxation techniques ofvoluntary muscles, a strong focus of attention, andspecific activities to concentrate on duringcontractions to block pain.• Presence of another woman during labor to supportthe expectant mother has a positive effect onoutcomes, including the duration of labor.
Transcutaneous Electrical NerveStimulation• TENS is thought to reduce pain by nociceptiveinhibition at a presynaptic level in the dorsal horn bylimiting central transmission.• Electrical stimulation preferentially activates low-threshold myelinated nerves.• Afferent inhibition effects inhibit propagation ofnociception along unmyelinated small c fibers byblocking impulses to target cells in the substantiagelatinosa of the dorsal horn.• TENS enhances release of endorphins anddynorphins centrally.• Placement of electrode pads over the lower backregion in the distribution of T10-L1 may providesome analgesia for parturients in early labor.
Therapeutic Use of Heat and Cold• Temperature (hot or cold) applied to variousregions of the body in this method.• Warm compresses may be placed on localizedareas, or a warm blanket may cover the entirebody.• Icepacks may be placed on the low back orperineum to decrease pain perception.• The therapeutic use of heat and cold duringlabor has not been studied in a rigorousscientific manner.
Hydrotherapy• Hydrotherapy involve a simple shower or tubbath, or it include the use of a whirlpool orlarge tub specially equipped for pregnantpatients.• Benefits of hydrotherapy includes reduced pain& anxiety, decreased BP & increased efficiencyof uterine relaxation.
Vertical Position• The vertical position is associated withdecreased pain, especially in early labor.• Length of labor is either unaffected ordecreased• No difference in the incidence of instrumentaldelivery.
Acupuncture/Acupressure• Derived from traditional Chinese medicine.• Effects on pain relieving is extremely variablebetween different ethnic groups.• It has not gained wide spread popularity andhence not studied rigorously.
Meperidine• Meperidine is the most commonly used parenteralopioid analgesic during labor.• im dose ranges from 50 to 100 mg with a peak onsetof effect at 40 to 50 minutes• iv doses of 25 to 50 mg start to act within 5 to 10minutes.• Analgesic effect lasts up to 3 to 4 hours.• Fetal exposure to meperidine is highest between 2and 3 hours after maternal administration.• Meperidine is cause less respiratory depression inthe neonate than morphine does.• It cause loss of beat-to-beat variability of FHRtracings.
Fentanyl• Short half-life makes fentanyl suitable for prolongeduse in labor, either as an intravenous bolus or as ananalgesic administered by means of a PCA deliverysystem.• It provides reasonable levels of analgesia with minimalneonatal depression.• The usual dose of fentanyl for labor analgesia is 25 to50 µg intravenously.• The peak effect occurs within 3 to 5 minutes and has aduration of 30 to 60 minutes.
Remifentanil• Potent, short-acting µ-opioid receptor agonist that hasa t1/2 of 1.3 min & prolonged administration does notcause accumulation of this drug.• PCA with intravenous remifentanil suggest that amedian effective bolus dose of 0.4 µg/kg with alockout time of 1 minute or a continuous infusion at0.05 µg/kg/min with a bolus of 25 µg and a lockouttime of 5 minutes provides satisfactory labor analgesia.• Fetal exposure to the drug is minimized because of itsrapid metabolism or redistribution, or both.• It is an attractive alternative systemic analgesic inparturients in whom regional anesthesia iscontraindicated.
Sedative-Tranquilizers• Sedative-tranquilizers, e.g. barbiturates,phenothiazines, hydroxyzine, and BZD, havebeen used for sedation, anxiolysis, or bothduring early labor and before cesarean delivery.• Promethazine is the most commonlyadministered phenothiazine in obstetrics. Usedwith meperidine, given in doses of 25 to 50 mgto prevent emesis. Its ability to potentiate theanalgesic effects of opioids, however, is indoubt.
Ketamine• Ketamine has been used in subanesthetic doses(0.5 to 1 mg/kg or 10 mg every 2 to 5 minutes to atotal of 1 mg/kg in 30 minutes) during labor.• ketamine in a dose of 25 to 50 mg can be used tosupplement an incomplete neuraxial blockade forcesarean section.• Its cause hypertension, tachycardia & emergencereactions.• High doses (>2 mg/kg) can produce psychomimeticeffects and increased uterine tone, which maycause low Apgar scores and abnormalities inneonatal muscle tone.
Inhaled Analgesia• Inhaled analgesia can be defined as the administrationof subanesthetic concentrations of inhaled anestheticsto relieve pain during labor.• It has limited efficacy, not solely effective for most of themothers.• Have a place as an adjunct to neuraxial techniques or inparturients in whom regional anesthesia is not possible.• Inhaled analgesics can be administered eitherintermittently (during contractions) or continuously.• They can be self-administered, but the patient shouldhave a health care provider present to ensure anadequate level of consciousness and proper use of theequipment.
Inhaled Analgesia• Entonox (50 : 50 N2O/O2 mixture) can be used as soleanalgesic and an adjuvant to systemic and regionaltechniques for labor.• Side effects include dizziness, nausea, dysphoria, and lackof cooperation.• The maximum analgesic effect occurs after 45 to 60seconds, and it is therefore important that the parturientuse Entonox at the early onset of her contractions anddiscontinue its use after the peak of the contraction.• Desflurane (0.2%), enflurane, and isoflurane (0.2% to0.25%) have also been used to provide labor analgesia bymeans of hypnosis.• The major risk when using volatile analgesics is accidentaloverdose resulting in unconsciousness and loss ofprotective airway reflexes.
Central Neuraxial Blockade• Epidural Analgesia• Spinal Analgesia/ Anesthesia• CESA
Epidural Analgesia/ Anaesthesia• “in the absence of a medicalcontraindication, maternal request is asufficient medical indication for painrelief during labor”- ASA & ACOG joindeclaration
Timing of Epidural Analgesia• Controversy exists regarding when it is appropriate tobegin epidural analgesia during labor in an individualpatient.• “Early” epidural analgesia (e.g., before 5 cm cervicaldilation) may interfere with uterine contractions andslow the progress of labor.• If a patient in early labor requests epidural analgesia,first administer either a spinal or epidural opioid aloneor an epidural opioid combined with a very dilutesolution of LA
Contraindications• Patient refusal or inability to cooperate• Increased intracranial pressure secondary to a masslesion• Skin or soft tissue infection at the site of needleplacement• Frank coagulopathy• Uncorrected maternal hypovolemia (e.g.,hemorrhage)• Inadequate training in or experience with thetechnique
Preparation for Epidural/ SpinalAnalgesia• The patient requests epidural analgesia for pain relief (or forrelief of anticipated pain ,planned induction of labor).• Preanesthetic evaluation, which includes an assessment of thepatients medical and anesthetic history.• The risks of epidural analgesia are discussed with the patient,and informed consent is obtained.• The obstetrician is consulted to confirm the following: That the patient is in labor and the obstetrician is committedto delivering the infant. That all relevant obstetric issues are understood (e.g.,gestational age, intrauterine growth restriction, fetalpresentation, risk of obstetric hemorrhage, previous cesareandelivery).• An assessment of fetal well-being is performed in consultationwith the obstetrician.
Resuscitation Equipments• DRUGS• Thiopental• Succinylcholine• Ephedrine• Atropine• Epinephrine• Phenylephrine• Calcium chloride• Sodium bicarbonate• Naloxone• EQUIPMENT• Oxygen supply• Self-inflating bag and mask forpositive-pressure ventilation• Masks• Oral and nasal airways• Laryngoscopes• Endotracheal tubes• Suction (including the necessarysupplies)• Intravenous catheters andfluids• Syringes and needles
Recommended Technique• Informed consent is obtained, and the obstetrician isconsulted.• Monitoring includes the following: Blood pressure every 1 to 2 minutes for 15 minutes aftergiving a bolus of local anesthetic; Continuous maternal heart rate monitoring duringinduction of anesthesia; Continuous fetal heart rate monitoring; and Continual verbal communication.• Pre-hydration with 500 mL of Ringers lactate solution.• Lateral decubitus or sitting position.• The epidural space is identified with a loss-of-resistancetechnique.• The epidural catheter is threaded 3 to 5 cm into theepidural space.
Recommended Technique• A test dose of 3 ml of 1.5% lidocaine with 1:200,000epinephrine is injected after careful aspiration and after auterine contraction.• If the test dose is negative, one or two 5-mL doses of 0.25%bupivacaine are injected to achieve a cephalad sensory level ofapproximately T10.• After 15 to 20 minutes, the block is assessed by means of loss ofsensation to cold or pinprick.• If no block is evident, the catheter is replaced.• If the block is asymmetric, the epidural catheter is withdrawn 0.5to 1.0 cm, and an additional 5 to 10 ml of the same bupivacainesolution is injected.• If the block remains inadequate, the catheter is replaced.
Recommended Technique• The patient is cared for in the lateral or semilateralposition to avoid aortocaval compression.• Subsequently, maternal blood pressure is measuredevery 5 to 15 minutes.• The fetal heart rate is monitored continuously.• The level of analgesia and the intensity of motor blockare assessed every 1 to 2 hours.
Maintenance of Epidural AnalgesiaINTERMITTENT BOLUS INJECTION• Single epidural injection of LAdoes not provide adequateanalgesia for the duration oflabor.• Exclude migration of theepidural catheter into a bloodvessel or the subarachnoidspace.• After several injections,blockade of the sacral segments,intense motor block, or bothmay develop.• Sensory level and the intensityof motor block should beassessed and recorded beforeand after each bolus injection oflocal anesthetic.CONTINUOUS EPIDURAL INFUSION• Benefits include:(1) themaintenance of a stable levelof analgesia;• stable maternal heart rate andblood pressure, & decreasedrisk of hypotension;• less frequent need to givebolus doses of LA, whichreduce the risk of LAST.• continuous epidural infusiontechnique does not obviate theneed for frequent assessmentof the patient.
Recommended Regimen for EpiduralDrug Intermittent injection Continuous infusionBupivacaine 5-10 mL of a 0.125%-0.375% solution every60-120 min0.0625%-0.25%solution given at arate of 8-15 mL/hrRopivacaine 5-10 mL of a 0.125%-0.25% solution every60-120 min0.125%-0.25%solution given at arate of 6-12 mL/hrLidocaine 5-10 mL of a 0.75%-1.5% solution every60-90 min0.5%-1.0% solutiongiven at a rate of 8-15 mL/hr
Patient Controlled Epidural Analgesia• With this technique, each patient can adjust her levelof analgesia.• PCEA has been associated with greater maternalsatisfaction as compared with both intermittent bolusinjectionand continuous epidural infusion.• PCEA results in a lower average hourly dose ofbupivacaine than does a continuous epidural infusionof bupivacaine.• Reserved for patients who are willing and able tounderstand that they are in control of their analgesia.
Analgesia for Second stage of labor• Require a more concentrated solution and/or a greatervolume of LA than is required during the first stage oflabor.• The continuous epidural infusion of bupivacaine oftenresults in the gradual development of sacral analgesia.• Additional bolus doses of LA can be required to augmentperineal analgesia.• Administration of a larger volume of LA solutionfacilitates the onset of sacral analgesia. This also resultsin a higher (i.e., more cephalad) sensory level ofanalgesia, and the patient should be observed forevidence of hemodynamic or respiratory compromise.
Analgesia in advanced labor• Advanced labor does not preclude the placement of alumbar epidural catheter, especially in a nulliparouswoman.• Another option is to administer combined spinal-epidural (CSE) analgesia.• A caudal epidural catheter, which facilitates the onset ofsacral analgesia, is an option for analgesia late in labor.Disadvantages are(1) increased technical difficulty; (2)increased LA dose requirement during the first stage;and (3) the risk of injecting the LA into the fetus.• Sacral analgesia adequate for labor and delivery can beachieved with an injection of 12 to 15 mL of 0.25%bupivacaine, 1.0% to 1.5% lidocaine.
Spinal Analgesia/ Anesthesia• Not very effective in laboring women.• A single-shot injection has a finite duration, and multipleinjections result in an increased risk of PDPH.• Single subarachnoid injection of an opioid may beappropriate.• A “saddle block” can be administered to achieveblockade of the sacral spinal segments; a small dose of ahyperbaric local anesthetic solution is adequate for thispurpose.• Placement of a catheter in the subarachnoid space is notrecommended by US FDA
Complications• Hypotension (Incidence 17-20%)• Inadequate Analgesia (0.5-1.5%)• Intravascular Injection of Local Anesthetic• Unintentional Dural Puncture (1-7.6%)• Unexpected High Block• Subdural injection of a local anesthetic (0.82%)• Extensive Motor Block• Urinary Retention• Back Pain: prospective studies have consistently shownthat no causal relationship exists between the use ofepidural analgesia and the development of long-termpostpartum backache.• Pelvic Floor Injury
Neonatal Outcome• Newborns whose mothers received epidural analgesiahad higher pH measurements and less metabolicacidosis in the first hour of life as compared withnewborns whose mothers received systemic opioidanalgesia.• No difference in neonatal outcome (as assessed byApgar scores and umbilical cord blood pHmeasurements).• No difference in long term neonatal outcome.
“Expectant mothers can be reassured that, althoughepidural analgesia may be associated with someshort term maternal side effects, it does notexacerbate fetal acidosis, and if anything, maypartially protect the fetus from fetal hypoxia. It isimportant to dispel the notion that epiduralanalgesia is in some way harmful to babies.”- ReynoldsF, Sharma SK, Seed PT: Analgesia in labor and fetal acid-base balance: A meta-analysis comparing epidural with systemic opioid analgesia. BJOG 2002; 109:1344-1353.
Neuraxial Opioid• Opioids block the transmission of pain-relatedinformation by binding at presynaptic andpostsynaptic receptor sites in the dorsal horn of thespinal cord (i.e., Rexed laminae I, II, and V), and in thebrainstem nuclei, periventricular gray matter, medialthalamus.• They are associated less adverse effects than systemicuse
Epidural Opioid• Opioid and a LA are given epidurally, they interactsynergistically to provide effective pain relief.• Epidural administration of an opioid alone providesmoderate analgesia during early labor, but the doseneeded to maintain analgesia is accompanied bysignificant side effects.• Epidural opioid alone provides inadequate analgesiaduring the advanced phase of the first stage of labor &during the second stage.
OPIOIDS USED TO PROVIDE EPIDURALANALGESIA DURING LABORDrugs Dose Onset (Minutes) Duration (hours)Morphine 3–5 mg 30–60 4–12Pethidine 25–50 mg 5–10 2–4Butarophanol 2–4 mg 10–15 6–12Fentanyl 50–100 μg 5–10 1–2Sufentanil 5–10 μg 5–10 1–3
INFUSION REGIMENS FOR CONTINUOUSEPIDURAL ANALGESIA DURING LABORDrug Bupivacaine-fentanyl Bupivacaine-butorphanolBupivacaine-sufentanilLoading doseBupivacaine 0.125%–0.25% 0.125%–0.25% 0.125%–0.25%Opioid 2µg/ml 2.5–5 μg/mL 0.2 mg/mLVolume 10–15 mL 10–15 mL 10–15 mLInfusionBupivacaine 0.125%–0.25% 0.0625%–0.125% 0.0625%–0.125%Opioid 1µg/ml 1–2 μg/mL 0.1 mg/mLRate 10–15 mL/hr 10–15 mL/hr 8–12 mL/hr
Intrathecal Opioids• rapid onset of pain relief• have a predictable duration of action• minimize undesirable side effects (e.g., motor block,hypotension)• preserve proprioception• have no effect on the fetus• Intrathecal opioids alone provide effective analgesiaduring early labor but they do not provide effectiveanalgesia during advanced labor.
Complications of Neuraxial Opioid• Pruritus• Neurotoxicity• Sensory Changes• Hypotension• Nausea and Vomiting• Respiratory Depression• Delayed Gastric Emptying• Recrudescence of Herpes Simplex ViralInfection• Postdural Puncture Headache
Fetal Effects of Opioid• Direct fetal effects may include intrapartumeffects on the FHR as well as possiblerespiratory depression after delivery.• Indirect fetal effects include fetal bradycardia.• Fetal bradycardia after labor analgesia doesnot appear to have a detrimental effect on theoutcome of labor.
Effects of analgesia on labor• Epidural analgesia to reduce uterine activity in somepatients, but it results in enhanced uterine activity inothers.• Duration alone is of little significance if labor pain isadequately controlled and fetal/neonatal well-being ispreserved.• Maintenance of total anesthesia prolongs the secondstage of labor.• Use of epidural analgesia results in a small increase inthe cesarean section rate.
Effects of analgesia on labor• Administration of a dilute solution of LA resultsin fewer cases of malposition of the vertex andfewer instrumental vaginal deliveries thanadministration of a more concentratedsolution.• Epidural analgesia was not associated with aprolonged third stage of labor.
Peripheral Nerve Blocks• In first stage of labor:1. Paracervical block2. Lumbar sympathetic block• In second stage of labor:1. Pudendal nerve block
Paracervical Block• This nerve plexus lies lateral & posterior to the junctionof uterus & cervix, at the base of broad ligament.• Patient position: Lithotomy with left uterinedisplacement.• Timing: First stage of labor, before the cervix is dilated 8cm.• Equipments: 12-14cm 22G needle/ Kobak needle withIowa trumpet.• Technique: Index & middle finger of right hand introducethe needle into the lateral fornix for the right side & vice-versa in the left, with lateral diversion, the afteraspiration deposit 10ml LA just beneath the epithelium.
Paracervical Block• Site of drug deposition:• Two 10ml at 3 & 9 o’clock cervical position• 3-5ml LA at four sites ( 4,5,7,8 o’clock position)• Six different injections, 3ml each• Contralateral injection should be given after 5 min or twouterine contraction.• Onset usually within 5 minute, failure rate between 5-13%• Lignocaine without adrenalin is the most preferred drug.Bupivacaine is NOT recommended for this block.• Complications include broad ligament hematoma, sciaticnerve block, parametritis, subgluteal & retropsoalabscess, neuropathy and LAST
Lumbar Sympathetic Block• Paravertebral lumbar sympathetic block interruptsthe transmission of pain impulses from the cervix andlower uterine segment to the spinal cord.• Lumbar sympathetic block provides analgesia duringthe first stage of labor but does not relieve painduring the second stage.• It provides analgesia comparable to that provided byparacervical block but with less risk of fetalbradycardia.
Lumbar Sympathetic Block• Technique• Patient in the sitting position• 10-cm, 22-gauge needle is used to identify thetransverse process on one side of the second lumbarvertebra. The needle is then withdrawn, redirected, andadvanced another 5 cm so that the tip of the needle isat the anterolateral surface of the vertebral column, justanterior to the medial attachment of the psoas muscle.• Two increaments of 5ml LA solution on each side ofvertebral column after careful negative aspiration.• Modest hypotension occurs in 5% to 15% of patients.
Pudendal Nerve Block• The pudendal nerve(S2-4) represents the primary source ofsensory innervation for the lower vagina, vulva, andperineum. It also provides motor innervation to the perinealmuscles and to the external anal sphincter.• Effective in relieving second stage labor pain.• Technique: Transvaginal (More popular)• A needle and needle guide is introduced into the vaginawith the left hand for the left side of the pelvis and withthe right hand for the right side. The needle isintroduced through the vaginal mucosa andsacrospinous ligament, just medial and posterior to theischial spine. The pudendal artery lies in close proximityto the pudendal nerve; thus the one must aspiratebefore and during the injection of LA.
Pudendal Nerve Block• A 7-10 ml LA is sufficient.• A diluted solution of any LA is safe & effective.• Maternal complications are uncommon, but can beLaceration of the vaginal mucosa, Vaginal andischiorectal hematoma, Retropsoal and subglutealabscess & LAST.• Fetal complications are rare. The primary fetalcomplications result from fetal trauma and/or directfetal injection of local anesthetic.
Postoperative Analgesia after LUCS• Epidural analgesia: Epidural opioid, LA orLA+Opioid• Intrathecal opioid• Systemic analgesic• Peripheral nerve block
Opioids in Postoperative Analgesia• Opioids can be given as intermittent im or ivinjection or continuous iv infusion.• PCA can also be an attractive options for thosewho are willing & educated.• Most important concern is the neonataleffects of opioids that secreted in breast milk.
Opioids & LactationAnalgesic Category Milk: plasma ratio Newborn toleranceButorphanol 3 1.9 (oral) 0.7(intramuscular)No reports of adverse effectsCodeine 3 2.5 Possible accumulationFentanyl 3 > 1 Well toleratedHeroin 3 > 1 Possible addictionHydromorphone — No data No dataMeperidine 3 1.4 Prolonged half-lifeMethadone 3 0.83 CAUTION: Withdrawal symptomspossible with abrupt cessationMorphine 3 0.23–5.07 Possible accumulationNalbuphine — No data No dataOxycodone — 3.4 Periodic sleeplessness; failure tofeedOxymorphone — No data No dataPentazocine — Minimal excretion No dataPropoxyphene 3 0.50 Poor muscle tone reported
• The effects of maternal medication can beminimized by giving attention to the followingprinciples:• (1) avoiding the administration of drugs with along plasma half-life;• (2) when possible, delaying drug administrationuntil just after an episode of breast-feeding;• (3) observing the neonate for abnormal signs orsymptoms (e.g., change in feeding or sleeppatterns, somnolence, decreased muscle tone,increased irritability);• (4) when possible, choosing drugs that have theleast potential for excretion into breast milk andaccumulation in the neonate or that are known tobe tolerated by the newborn.
“The American Academy of Pediatrics Committeeon Drugs lists butorphanol, codeine, fentanyl,methadone, and morphine as maternallyadministered opioids that typically arecompatible with breast-feeding.”- American Academy ofPediatrics Committee on Drugs.: The transfer of drugs and otherchemicals into human milk. Pediatrics 2001; 108:776-789
NSAID• They reduce opioid consumption by thepatient.• NSAIDs reduce the inflamatory pain.• Acitamenophen, Ibuprofen, Aspirin,Ketorolac & Diclofenac are designated asCategory 3 drug by AAP, so they are welltolerated.