Perioperative Ketorolac-lidocaine in the Patients With Valvular Heart Diseases During Cesarean Delivery

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Mansoura University
Sponsor:
Information provided by (Responsible Party):
Mohamed R El Tahan, Mansoura University
ClinicalTrials.gov Identifier:
NCT01571791
First received: March 31, 2012
Last updated: October 30, 2012
Last verified: October 2012
  Purpose

Rheumatic heart valve diseases are prevalent among the young people in Egypt secondary to the socioeconomic conditions. The goal of anesthetic management of these patients is maintenance of sinus rhythm, systemic blood pressure, preload, coronary perfusion, and cardiac output. Many women still prefer general anesthesia rather than regional techniques at the author's country.

The pharmacological modifications of the sympathetic response to tracheal intubation and surgical stimulation using opioids have adverse effects on the neonatal outcome after cesarean delivery. The authors have demonstrated in their previous studies the safety of both perioperative infusion of both of ketorolac and lidocaine in the attenuation of the hemodynamic and hormonal responses of tracheal intubation and surgery during cesarean delivery with favorable neonatal outcome and without added risk of perioperative bleeding. Therefore, the authors reported successful anesthetic management of a parturient with infective endocarditis on top of rheumatic mitral valve disease with use of paracetamol-lidocaine-ketorolac-propofol anesthesia.

The investigators hypothesize that the perioperative use of ketorolac-lidocaine would reduce the maternal hemodynamic responses to intubation and surgery without any harmful effects on mother or baby during uncomplicated cesarean delivery in the parturients with valvular hear diseases.

The investigators are aiming to compare the effects of ketorolac-lidocaine and fentanyl on surgical stress responses, intraoperative fentanyl and vasoactive drugs consumption and neonatal outcome during cesarean delivery in the parturients with valvular hear diseases.


Condition Intervention Phase
Valve Heart Disease
Elective Cesarean Delivery
Drug: Placebo
Drug: Ketorolac-Lidocaine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Study of the Effects of Perioperative i.v. Ketorolac-lidocaine on the Hemodynamic Response in the Patients With Valvular Heart Diseases During Cesarean Delivery

Resource links provided by NLM:


Further study details as provided by Mansoura University:

Primary Outcome Measures:
  • hemodynamics [ Time Frame: Baseline, intraoperative, an expected average of 1 hour ] [ Designated as safety issue: Yes ]
    changes in blood pressures and heart rate


Secondary Outcome Measures:
  • changes in fentanyl consumption [ Time Frame: intraoperative, an expected average of 1 hour ] [ Designated as safety issue: No ]
    Intraoperative fentanyl consumption

  • perioperative bleeding [ Time Frame: intraoperative, an expected average of 1 hour, up to 24 hours after surgery ] [ Designated as safety issue: Yes ]
    Intra-operative blood loss will be assessed by measuring blood in the suction bottle minus the sonographically estimated amniotic fluid volume, visual estimate of blood on drapes and floor and weighing swabs after use. Postoperative transfusion requirements and blood loss will be estimated as previously reported by Huang et al. from inspection of the perineal pad (0: small; 1: moderate; 2: large). Haematocrit values will be recorded before and 48 h after surgery.

  • neonatal outcome [ Time Frame: up to 24 hours after delivery ] [ Designated as safety issue: Yes ]

    Neonatal umbilical artery and umbilical vein blood pH, gas tensions, and base excess values.

    Apgar scores at 1 and 5 min, and newborns' blood pressure, heart rate, temperature, arterial oxygen saturation, and the Neurologic and Adaptive Capacity Score (NACS) will be recorded at 15 min, 2 and 24 h after delivery.


  • uterine tone [ Time Frame: intraoperative, an expected average of 1 hour ] [ Designated as safety issue: Yes ]
    The obstetrician will assess uterine tone by palpation every 5 minutes after delivery of the placenta using a 10-cm VAS (0: well contracted; 10: completely relaxed). If uterine tone remains unsatisfactory after 3 min, an additional 5 U bolus of oxytocin will be administered.

  • postoperative pain [ Time Frame: up to 24 after surgery ] [ Designated as safety issue: No ]
    a 10-cm VAS at rest and on movement (0: no pain; 10: worst pain imaginable) 0, 1, 2, 4, 6, 8, 10 and 12 h after surgery. For postoperative pain relief intravenous 100 mg will be given when VAS scores are 5 or more at rest, or 7 or more on movement, or if the patient requests additional analgesia. The time to first request for analgesia and the number of subjects receiving tramadol during the first 12 h will be recorded.

  • perioperative side effects [ Time Frame: up to 24 after surgery ] [ Designated as safety issue: Yes ]
    perioperative side effects includes arrhythmia, sedation, nausea and vomiting, light-headedness, headache, perioral numbness, tunnel vision, or seizures


Estimated Enrollment: 90
Study Start Date: June 2011
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: group SF
either saline infusion and intravenous fentanyl boluses
Drug: Placebo
to receive saline infusion and intravenous fentanyl boluses, at 30 min before induction of anesthesia
Active Comparator: group KL
ketorolac-lidocaine infusion and intravenous saline boluses
Drug: Ketorolac-Lidocaine
receive ketorolac-lidocaine infusion and intravenous saline boluses , at 30 min before induction of anesthesia

Detailed Description:

All parturients will receive oral ranitidine 150 mg on the night and the morning of surgery and 30 mL of 0.3 mol/L sodium citrate, 15 min before induction.

All operations will be performed by the same obstetricians. Voluven 6% solution 7 mL/kg will be infused over 30 min. Left uterine displacement will be maintained before induction. All routine medications except angiotensin-converting enzyme inhibitors will be continued until the morning of the operation.

All patients will be monitored with pulse oximetry, non-invasive blood pressure and five leads electrocardiography (leads II and V5). A radial artery catheter and a central venous catheter will be placed under local anesthesia before induction. On-screen pressure tracing will be used to determine end-expiration, and the CVP will be averaged over three respiratory cycles to eliminate respiratory artifacts. All staff in the operating room will be unaware of the randomization code.

After pre-oxygenation for 5 min, a rapid sequence induction will be performed with propofol 1-2.5 mg/kg and suxamethonium 1.5 mg/kg. Cricoid pressure will be applied, laryngoscopy will be performed after the 1-min blood pressure recording, and tracheal intubation will be completed before the 2-min reading. Anesthesia will be maintained with end-tidal concentrations of 2-2.5% of sevoflurane, in combination with 50% nitrous oxide in oxygen and cisatarcurium 0.1-0.2 mg/kg. The patients' lungs will be ventilated to maintain an EtCO2 of 4-4.6 kPa.

After the umbilical cord was clamped, infusion of 5-10 U oxytocin, midazolam 0.05 mg/kg and fentanyl 1-2 µg/kg will be given and nitrous oxide will be increased to 70%. Sevoflurane will be discontinued at the start of skin closure and the nitrous oxide will be discontinued after the last skin suture will be applied. At the end of surgery, residual neuromuscular block will be antagonized with neostigmine 50 µg/kg and atropine 20 µg/kg, and trachea will be extubated.

Intraoperative hypertension, defines as increase in mean arterial blood pressure (MAP) >= 25% of baseline for more than 1 min, with or without associated tachycardia (defined as HR value > 20% of the baseline value > 2 min) will be treated with IV boluses of fentanyl (1μg/kg). If blood pressure levels do not reach at least 20% of baseline levels after 5 min, slow intravenous administration of labetalol 20 mg will be considered. In the presence of hypotensive episodes (MAP decreased to <= 60 mmHg >= 2-3 min) and CVP < 8 mmHg, 5-7 ml/kg of 6% hydroxyethyl starch 130/0.4 will be given. In the presence of MAP ≤ 60 mmHg, and CVP > 10 mmHg, repeated bolus doses of ephedrine 5 mg will be given 5 min apart from each dose. Tachycardia ≥ 20% from the baseline values for ≥ 1 min will be treated with boluses of esmolol 20 mg.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 90 ASA II & IV women
  • with documented valvular heart disease
  • uncomplicated
  • singleton pregnancies of at least 36 weeks' gestation
  • scheduled for elective cesarean delivery
  • under general anesthesia

Exclusion Criteria:

  • history of un-controlled hypertension
  • ischemic heart disease
  • left-ventricular ejection fraction less than 45%
  • severe pulmonary hypertension
  • critical aortic stenosis
  • peripheral vascular disease
  • thyrotoxicosis
  • neurological diseases
  • hepatic diseases w
  • renal diseases
  • allergy
  • those requiring preoperative inotropic, vasopressor,
  • mechanical circulatory or ventilatory support
  • pregnancy-induced hypertension
  • evidence of intrauterine growth restriction
  • fetal compromise.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01571791

Contacts
Contact: Mohamed R El Tahan, M.D. +966 56 9371849 mohamedrefaateltahan@yahoo.com

Locations
Egypt
Mansoura University Hospitals Recruiting
Mansoura, DK, Egypt, 050
Contact: Eiad A Ramzy, M.D.    +201005774079    eiadramzy@yahoo.com   
Sponsors and Collaborators
Mansoura University
  More Information

No publications provided

Responsible Party: Mohamed R El Tahan, Principal Investigator, Mansoura University
ClinicalTrials.gov Identifier: NCT01571791     History of Changes
Other Study ID Numbers: R/41
Study First Received: March 31, 2012
Last Updated: October 30, 2012
Health Authority: Egypt: Ministry of Higher Education

Keywords provided by Mansoura University:
Ketorolac
lidocaine
valvular hear diseases
cesarean section

Additional relevant MeSH terms:
Heart Diseases
Heart Valve Diseases
Cardiovascular Diseases
Lidocaine
Ketorolac
Ketorolac Tromethamine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014