Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03091881 |
| Other study ID # |
2978 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2018 |
| Est. completion date |
November 1, 2018 |
Study information
| Verified date |
June 2022 |
| Source |
Suez Canal University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Diabetic Parturients are exposed to intraoperative hypotension after spinal anesthesia and we
proposed that intravenous Granisterone 1 mg will attenuate the hypotension occurred with
spinal block during Cesarean sections.
Description:
Introduction:
Spinal anesthesia is considered the first choice for cesarean sections if there are no
absolute or relative contraindications. It is easy and has lower risks for mother and baby
for most of cases. Anesthetists, especially junior staff, prefer spinal anesthesia for
cesarean sections avoiding managing airway or inserting an endotracheal tube which is usually
difficult in full term pregnant woman.
Hypotension that follows spinal anesthesia usually occur due to blockade of sympathetic
vasomotor activity that is accentuated by compression of the aorta and inferior vena cava by
the gravid uterus when the patient is in the supine position.
It starts very soon after intrathecal injection of the local anesthetic and may extend till
the end of the block putting the anesthesia team in an explanatory situation. The
pathophysiology of spinal hypotension is mainly due to the sympathetic blockade predominating
pararsympathetic power to dilating blood vessels and subsequent blood pooling in the dilated
blood vessels (mainly venous side).
Sudden bradycardia can occur from shift in cardiac autonomic balance toward the
parasympathetic system from activation of left ventricular mechanoreceptors or chemoreceptors
Bezold Jarisch reflex (BJR) or from an increase in baroreflex activity.[1] Serotonin released
during low-volume states has been suggested as a possible trigger for the BJR.[2] Granisetron
is a 5-Hydoxy Tryptamine 3 (5-HT3) receptor antagonist that is very effective in preventing
nausea and vomiting.
Diabetes mellitus is a widespread disease that increases the risk of cardiovascular diseases
and intraoperative mortalities. Diabetes is associated with increased risk of perioperative
hypotension due to autonomic neuron system dysfunction associated with micro and macro
complications of long standing hyperglycemia. The effect of preganglionic sympathetic fibers
and cardiac sympathetic innervation blockade occurring during spinal anesthesia on cardiac
autonomic neurons function are expected to be different in diabetic patients from that of
normal patients.
In a large cohort of patients with type 1 and type 2 diabetes, Ziegler et al. [3], using
predefined heart rate variability (HRV) tests and spectral analysis of the R-R intervals,
found that 25.3% of patients with type 1 diabetes and 34.3% of patients with type 2 diabetes
had abnormal findings. Clinical symptoms of autonomic dysfunction may not appear until long
after diabetes onset.
However, subclinical cardiac neuropathic dysfunction, manifested as changes in HRV, may be
detected within 1 year of diagnosis in type II diabetes and within 2 years of diagnosis in
type I diabetes .[4]
The incidence of hypotension defined as systolic blood pressure less than 90 mm Hg and
bradycardia defined as heart rate less than 50 beat/minute are haemodynamic adverse effects
of spinal anesthesia in non-obstetric patients has been reported to be 33% and 13%
respectively.[5,6]
Aim of the work:
This study will investigate the effect of the antiemetic drug Granisetron (G Setron 1 mg in 1
ml ampule) in reducing the incidence of hypotension occurred with spinal anesthesia in type I
diabetic patients arranged for cesarean sections.
Material and Methods:
This study will be randomized double blind where the anesthetists', data collectors and
patients will be blinded to the assigned groups.
After hospital ethics committee approval and written informed consents, 68 type I diabetic
patients scheduled for cesarean sections will participate in this study at Operation Theater
of Suez Canal University Hospitals. All participating patients will be randomly classified
into two equal groups, the (G) Granisetron group and the (P) Placebo group.
The primary outcome will be the incidence of Hypotension defined as SBP < 90 mmHg occurred
with spinal anesthesia in type I diabetic patients arranged for caesarean sections.
A total of 68 type I diabetic full term pregnant women enrolled for caesarean section
deliveries under spinal anesthesia will be included in this study. Approval of our
institutional medical committee and a written consent from patients will be obtained.
Inclusion criteria will include diabetic (Type I) ladies aged above 21 years old arranged for
elective caesarean section under spinal anesthesia. Exclusion criteria will include any
contraindications for spinal anesthesia (like bleeding diathesis or regional infection at
site of neuroaxial block), known allergy to Granisetron or local anaesthetic (heavy
bupivacaine, Marcaine Spinal 0.5% Heavy, 5mg/ml, AstraZeneca ampule), chronic hypertension,
pregnancy induced hypertension, or congenital or rheumatic heart diseases, antepartum
haemorrhage, Fetal destress or gestational age < 36 week.
All patients will be randomly classified in to two equal groups (34 patients in each): G
group will receive 1 mg Granisetron (G Setron, 1 mg/ml Egyptian Pharmaceutical Company)
intravenously diluted in 10 ml normal saline 10 minutes before spinal anesthesia, and P group
will receive 10 ml normal saline N.S as placebo considering the same timing and color of
solution. Randomization will be performed using a computer based random number generator and
sealed envelopes will not be opened till an informed consent is obtained. The study will be
double-blind as the anesthetists, data collectors and patients will not know the assignment
groups. The syringes of Granisetron and placebo will be prepared by an anesthetist who will
not be informed about the study protocol.
All patients will be infused with 500 ml lactated ringer intravenously IV. Premedication with
30 ml of a 0.15 molar solution of sodium citrate will be given orally 15-30 minutes before
surgery in addition to Ranitidine ampule (Zantac) 50 mg diluted in 10 ml N.S given
intravenously slowly. Base line heart rate (HR) and mean arterial blood pressure (MABP)
readings will be measured just before spinal anesthesia. Spinal anesthesia will be performed
in the sitting position using 25-gauge spinal needle (B BRAUN Co.) in L3-L4 or L4-L5 lumbar
interspaces, 12.5 mg (2.5 ml volume) 0.5% hyperbaric Bupivcaine (Marcaine Spinal 0.5% Heavy,
5mg/ml, AstraZeneca ampule) will be injected intrathecally over 1 minute. After spinal
anesthesia, parturient will be placed on the operating table in the supine position with 15°
of left lateral tilt with supplemental oxygen through a face mask at 5 L per min.
Sensory level will be evaluated by testing for cold sensation, and motor block will be
assessed according to Bromage scale after 5 min. HR and mean arterial blood pressure will be
recorded every 3 min until the end of surgery.
Blood pressure will be measured every 3 min Ephedrine 10 mg boluses will be used until
hypotension (Mean blood pressure above 65 mmHg) is controlled and then the predetermined
protocol will be followed.
Maintenance fluid of lactated Ringer's solution will be given at a rate of 10 ml/kg/h in both
groups during the surgical procedure. An additional rapid bolus infusion (100 ml) of lactated
Ringer's will be pushed at each episode of hypotension. 10 mg ephedrine will be administered
if MBP is less than 65 mmHg. A second dose of 10 mg ephedrine will be repeated if hypotension
persisted 5 min or recurred. Phenylephrine will be considered if persistent hypotension not
responding to ephedrine. If bradycardia occurred defined as HR lower than 60 beat per min 0.5
mg atropine will be considered unless it is associated with hypotension, if that ephedrine
will be the choice.
Demographic data of all patients (Age, Height, Weight, BMI, duration of procedure, duration
of diabetes, Glycosylated Hemoglubin, and parity) will be recorded. Incidence of hypotension
will be calculated and compared in both groups. Other useful information as incidence of
bradycardia (HR< 50 beat/minute) and atropine, ephedrine, and phenylephrine administered
doses will be recorded.
Nausea and vomiting will be recorded using Verbal Descriptive Scale (VDS) [0 = no nausea, 1 =
mild nausea, 2 = moderate nausea, 3 = frequent vomiting and 4 = severe vomiting] [7]
References
1. Butterworth J. Physiology of spinal anesthesia: What are the implications for
management? Reg Anesth Pain Med 1998;23: 370-3.
2. Adams VR, Valley AW. Granisetron: The second serotonin-receptor antagonist. Ann
Pharmacother 1995;29:1240-51.
3. Ziegler D, Dannehl K, Mühlen H, Spüler M, Gries FA. Prevalence of cardiovascular
autonomic dysfunction assessed by spectral analysis, vector analysis, and standard tests
of heart rate variation and blood pressure responses at various stages of diabetic
neuropathy. Diabet Med 1992; 9: 806- 814 [PubMed]
4. Pfeifer MA, Weinberg CR, Cook DL, Reenan A, Halter JB, Ensinck JW, Porte D., Jr
Autonomic neural dysfunction in recently diagnosed diabetic subjects Diabetes Care 1984;
7: 447- 453 [PubMed]
5. Carpenter RL, Caplan RA, Brown DL, Stephenson C, Wu R (1992) Incidence and risk factors
for side effects of spinal anesthesia.Anesthesiology 76: 906-916.
6. Arndt JO, Bömer W, Krauth J, Marquardt B (1998) Incidence and time course of
cardiovascular side effects during spinal anesthesia after prophylactic administration
of intravenous fluids or vasoconstrictors.Anesth Analg 87: 347-354.
7. Rhodes VA, Watson PM, Johnson MH. Development of reliable and valid measures of nausea
and vomiting. Cancer Nurs.1984;7:33-41
