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EFFICACY OF LOW DOSE PROPOFOL FOR CONTROL OF EMETIC

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EFFICACY OF LOW DOSE PROPOFOL FOR CONTROL OF EMETIC Powered By Docstoc
					RUDRA, HALDER, SEN, KUNDU:: 31-34DOSE PROPOFOL FOR EMETIC EPISODES
Indian J. Anaesth. 2004; 48 (1) LOW                                                                                                   31



             EFFICACY OF LOW DOSE PROPOFOL FOR CONTROL
             OF EMETIC EPISODES DURING CAESAREAN DELIVERY
                        WITH SPINAL ANAESTHESIA
                           Dr. A. Rudra 1 Dr. R. Halder 2 Dr. A. Sen 3 Dr. S. Kundu 4

SUMMARY
Nausea and vomiting during caesarean delivery under spinal anaesthesia are distressing to the patients and are a disturbance to the
surgeon. The aim of this study was to evaluate the efficacy of propofol at subhypnotic dose (1 mgkg-1hr-1) for reducing emetic symptoms
in women undergoing caesarean delivery under spinal anaesthesia. In a prospective, randomized, double-blind, placebo controlled
manner, we have compared the antiemetic efficacy of propofol with intralipid as placebo (n = 30 in each group) administered
immediately after clamping of the umbilical cord. Emetic episodes were noted and safety assessments were performed during spinal
anaesthesia for caesarean delivery. The degree of nausea was assessed by the patients using a visual analogue scale. The incidence
of patients experiencing no emetic symptoms in the intraoperative, postdelivery period was 86% with propofol and 40% with placebo
(P < 0.05). No clinically important adverse events caused by the study agents were observed. We conclude that propofol, given at
subhypnotic dose (1.0 mgkg-1hr-1) significantly decreases the incidence of emetic episodes in patients undergoing caesarean delivery with
spinal anaesthesia without clinically important adverse events in any of the groups.
Keywords : Complications : Nausea, Vomiting, Pharmacology : Antiemetic, Intravenous propofol, Anaesthesia : Obstetric,
Regional, Spinal.

Introduction                                                            vomiting in elective caesarean section under spinal
        The incidence of nausea-vomiting during and                     anaesthesia with hyperbaric 0.5% bupivacaine. Intralipid
immediately after caesarean delivery with spinal anaesthesia            10% was chosen as placebo, being the excipient of propofol,
are common occurrence and an annoying problem to all                    it is indistinguishable from the drug and has proved to be
concerned.1,2 In an attempt to decrease the incidence of                devoid of antiemetic and emetogenic effects.8
nausea-vomiting in these patients, a number of antiemetics
have been studied, which although effective, posses                     Material and methods
clinically significant side effects. Therefore, the condition                  After obtaining institutional ethical committee
remains a challenge for anaesthesiologists.                             approval and written informed consent from the patients,
       Propofol has been used successfully at subhypnotic               60 women of ASA physical status I or II, scheduled for
doses (0.5 – 1.0 mgkg-1hr-1) for the prevention and treatment           caesarean delivery with spinal anaesthesia, were enrolled
of chemotherapy induced emesis3,4 and to treat postoperative            in the study. Patients with contraindications for regional
nausea, vomiting without any side effects.5,6 However, a                anaesthesia and/or with a history of sensitivity to the
bolus injection of low dose (10 mg) propofol is not effective           drugs used in the study, patients who had gastrointestinal
for the prevention of nausea, vomiting during caesarean                 diseases, ear diseases, liver diseases or hyperemesis
delivery because of the short duration of action of propofol            graviderum, hyperlipidaemia and those who have received
administered.7 Therefore, we designed a prospective,                    drugs with antiemetic properties within 24 hours before
randomised, double blind, placebo-controlled, clinical                  surgery were not included in the study. Foetal pre-maturity
investigation to assess the effectiveness of subhypnotic                (less than 36 weeks gestation) was also considered a
dose (1.0 mgkg-1hr-1) infusion of propofol for prevention               contraindication for the study.
of intraoperative and early postoperative nausea and                           All patients received premedication with
 1.   M.D., FAMS; Professor and Head
                                                                        tab. ranitidine 150 mg orally the night before, and 90
 2.   M.D., Consultant Anaesthesiologist                                minutes before surgery. On arrival in the operating room,
 3.   M.D., Assistant Professor                                         routine monitoring devices were attached, and baseline
 4.   M.D., Consultant Anaesthesiologist                                blood pressure, heart rate, ECG, and pulse oximetry values
      Dept. of Anaesthesiology                                          were recorded. Each patient received 20 mlkg-1 of Ringer’s
      Calcutta National Medical College, 32 Gorachand Road,             lactate solution before spinal anaesthesia.
      KOLKATA – 700 014 (W.B.)
      Correspond to :                                                          Dural puncture was performed at the L3-L4 interspace
      Dr. A. Rudra                                                      with a 25 gauge lumbar puncture needle in right lateral
      (Accepted for publication on 22-10-2003)
                                                                        decubitus position. After the free flow of cerebrospinal
32                                                               INDIAN JOURNAL OF ANAESTHESIA, FEBRUARY 2004


fluid 2 ml of 0.5% hyperbaric bupivacaine (10 mg) was          0 (no nausea, no sedation) to 10 (severe nausea, extreme
injected intrathecally. Patients were placed in supine         sedation). The details of any other adverse effects due to
position with a 15° wedge under right buttock for left         the study agent were recorded by the attending
uterine displacement. Oxygen 3 litres per minute was           anaesthesiologist who interviewed the patients and
administered to the patients via face mask. Following          recorded their spontaneous complaints. Statistical analysis
confirmation of sensory block by loss of sensation to cold     of data between the groups were performed by ANOVA
and pinprick to T4-T5 level, surgery was started. Oxytocin     with Bonferroni’s correction for multiple comparison and
(10 units) was administered intravenously at the time of       chi-square test. A P value of less than 0.05 was regarded
umbilical cord clamping. ECG lead II, SpO2, pulse rate,        as statistically significant. All values were expressed as
respiratory rate and arterial blood pressure were monitored    mean ± SD, number (%), or median (range). Sample size
and recorded. The decrease in systolic blood pressure          was predetermined by using a power analysis based on the
(more than 20% baseline values and/or less than 90 mmHg)       assumption that 30 patients per group would be required
after spinal injection was treated by increasing the rate of   to demonstrate a 30% difference in values for an emesis
intravenous fluid administration, by exaggerating the          free episode at a=0.5 with a power b=0.8.
uterine tilt, and by 5-10 mg increments of ephedrine
administered intravenously (every 3-5 minutes) until           Results
resolution of hypotension.                                             There were thirty patients in each of the two study
                                                               groups and the data obtained from them were analysed.
        Patients were randomly assigned into one of the
                                                               Age, weight, gestational age, parity, blood pressure, heart
two groups (n=30 each) using a computer generated
                                                               rate, and rate of respiration were not different between the
randomization chart to receive either a continuous infusion
                                                               groups (table-1). The level of anaesthesia was considered
of propofol at a subhypnotic dose (1.0 mgkg-1hr-1 ) or
                                                               sufficient for the surgical procedure as an adequate sensory
placebo (10% intralipid) through a ‘T’ connector attached
                                                               block up to T4 was documented in all patients. The amount
directly to the venous cannula. Study agents were infused
                                                               of ephedrine used for the treatment of hypotension was
using a programmable syringe pump and was started
                                                               similar between the groups (table-2). In the intraoperative
immediately after clamping of the umbilical cord. The
                                                               and early post delivery period, 26 of 30 patients (86%)
study was carried out in a double-blind manner: only the
                                                               who had received propofol remained emesis free, compared
attending anaesthesiologist, but neither the patient nor the
                                                               with 12 of 30 (40%) who had received placebo (P <
observer during the study period knew which study agent
                                                               0.05). The severity of nausea was less in patients who had
had been used. The reports of clinical investigations by
                                                               received propofol 1.0 mgkg-1hr-1 than in those who had
Ewalenko et al.9 has interested us to choose the dose of
                                                               received placebo (P < 0.05). However, there was no
propofol (1.0 mgkg-1hr-1) in the current study. Ewalenko
                                                               difference in the level of sedation observed between the
et al have shown that propofol in the dose we have studied
                                                               groups (table-3). After discontinuation of the study agent,
can effectively reduce the incidence of postoperative nausea
                                                               all patients were wide awake. None of the patients of
and vomiting after thyroidectomy.9
                                                               either group complained of pain at the site of administration
       Intraoperative, post-delivery emetic episodes           of propofol or placebo.
(nausea, retching, vomiting) experienced by the patients
were recorded by anaesthesiologists blinded to the drug         Table - 1 : Maternal demographics
the patients had received. Episodes were identified by
direct questioning or by spontaneous complaint by the                                           Propofol (n = 30)   Placebo (n = 30)

patients. Nausea was defined as a subjectively unpleasant       Age (yrs)                            26 ± 4             23 ± 4
sensation associated with awareness of the urge to vomit;
                                                                Weight (kg)                          52 ± 6             54 ± 4
retching was defined as the laboured, spasmodic, rhythmic
contraction of the respiratory muscles without the expulsion    Gestational age (week)               39 ± 1             39 ± 1
of gastric contents; vomiting was defined as the forceful
                                                                Multiparous (n)                        10                 12
expulsion of gastric contents from the mouth.10 If two or
more episodes of nausea-vomiting occurred, 10 mg of             Baseline blood pressure
metoclopramide was provided intravenously as rescue             (mm Hg)                             112 ± 14           114 ± 12

antiemetic treatment. At the completion of surgery, the         Heart rate (min)                     80 ± 2             78 ± 4
patients were evaluated for the severity of nausea. Sedation
                                                                Respiratory rate (min)               16 ± 1             16 ± 1
was assessed by the anaesthesiologists. These evaluations
were performed with a linear numerical scale ranging from       Values are mean ± SD or number of patients
RUDRA, HALDER, SEN, KUNDU : LOW DOSE PROPOFOL FOR EMETIC EPISODES                                                                             33



 Table - 2 : Operative management                                              Ostman et al8 found that intralipid (the soya-oil emulsion
                                                                               in which propofol is formulated) posses no significant
                                        Propofol (n = 30)   Placebo (n = 30)   antiemetic effects. Thus intralipid is a valid placebo for
                                                                               propofol, particularly in the context of emesis investigations.
Duration of surgery (min)                    52 ± 4              54 ± 3
                                                                               The success rate with placebo in our study is also in
Uterus exteriorized (n)                         27                  28         accordance with the rate quoted in the literature.11
Duration of uterus exteriorized (min)        15 ± 3              16 ± 3                Many factors in the preoperative and peroperative
Hypotension (n)                             18 (60%)            16 (53%)       period may contribute to postoperative nausea and vomiting
                                                                               and, if these factors were not correctly taken into account,
Total ephedrine dose (mg)                     6 ± 3               6 ± 3        may introduce bias in the interpretation of results.9,12 We
 Values are mean ± SD or number of patients                                    found no difference in the preoperative state of patients or
                                                                               in their peroperative and postoperative courses. As our
Table - 3 : Number of patients free of symptoms or experiencing                patients represented a very homogeneous population,
nausea, retching, vomiting and requiring rescue antiemetic                     therefore, in the current study, any difference in the
medication                                                                     occurrence of emetic symptoms may reasonably be
                                                                               attributed to the study drug.
                                   Propofol (n = 30)        Placebo (n = 30)
                                                                                      Factors attributing to nausea-vomiting during
 (0-3 hrs after anaesthesia)
                                                                               caesarean delivery under spinal anaesthesia include
 Emesis-free                            26 (86%)*              12 (40%)        peritoneal traction, exteriorisation of uterus, fundal pressure
                                                                               during delivery of the baby and/or hypoxia associated with
 Nausea                                  2 (7%)                 9 (30%)
                                                                               hypotension following spinal anaesthesia.17,18
 Retching                                2 (7%)                 7 (23%)
                                                                                       The results in the present study suggested that
 Vomiting                                2 (7%)                 7 (23%)        patients who had received propofol at subhypnotic dose
 Rescue                                  3 (10%)               11 (37%)
                                                                               (1.0 mgkg-1hr-1) provide significant emesis-free period than
                                                                               in those who had received placebo during caesarean delivery
 Severity of nausea (VAS)                0 (0-6)*                0 (0-9)       under spinal anaesthesia. The exact mechanism by which
 Sedation (VAS)                          1 (0-5)                 1 (0-5)
                                                                               propofol prevents emesis is not known. It has been
                                                                               postulated that antiemetic effects of propofol may be as an
 Values are number(%) of patients or median (range)
 *P value < 0.05                                                               antagonist at the 5-HT3 receptor.15,16 However, Borgeat
                                                                               et al3 suggested that the antiemetic effect of propofol may
Discussion                                                                     be due to modulation of subcortical pathways. In this study,
         Nausea and vomiting are appreciably high in                           sedation level was comparable among the treatment groups,
caesarean section with spinal anaesthesia, especially when                     and, there were no clinically important adverse events in
no prophylactic antiemetic is provided.1,2 In this clinical                    any of the groups.
study, however, the treatment groups were similar with
regard to maternal demographics and operative                                          We conclude that propofol at subhypnotic dose
management, and patients with a history of motion sickness/                    (1.0 mgkg-1hr-1) could provide significantly better prevention
or previous history of emesis after operation, or diseases                     of emetic episodes than placebo during and the early hours
initiating emesis were excluded because they had a relatively                  after caesarean section performed under spinal anaesthesia
high incidence of emetic symptoms.9 Otherwise, the number                      with 0.5% hyperbaric bupivacaine.
of patients who were emesis free observed in the present                       References
study would be changed if such patient related factors
                                                                               1. Lussos SA, Bader AM, Thornhill ML, Datta S. The antiemetic
were not controlled. In the current study, 60% patients                           efficacy and safety of prophylactic metoclopramide for elective
receiving placebo have shown emesis, and that was in                              cesarean section delivery during spinal anesthesia. Reg Anesth
agreement with the study reports of previous workers.1,2                          1992; 17: 126-30.
However, 14% of patients who had received propofol at                          2. Santos A, Datta S. Prophylactic uses of droperidol for control
a subhypnotic dose (1.0 mgkg-1hr-1) have shown emesis.                            of nausea and vomiting during spinal anesthesia for caesarean
Moreover, the studied subhypnotic dose of propofol was                            section. Anesth Analg 1984; 63: 85-7.
not only superior in comparison with placebo to control                        3. Borgeat A, Wilder-Smith OH, Forni M, Suter PM. Propofol
the incidence of emesis, but also without unwanted                                improves patient comfort during cisplatin chemotherapy. A
sedative, respiratory or cardiovascular side effects. Recently,                   pilot study. Oncology 1993; 50: 456-459.
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4. Scher CS, Amar D, McDowall R, Barst SM. Use of propofol                            relations to patients characteristics, anaesthetic routines
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5. Borgeat A, Wilder-Smith OH, Saiah M, Rifat K. Subhypnotic                      13. Datta S, Alper MH, Ostheimer GW, Weiss JB. Methods of
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6. Sculman SR, Rockett CB, Canada AT, Glass PSA. Long term                            56: 68-70.
    propofol infusion for refractory postoperative nausea : a case                14. Patra CK, Badola RP, Bhargava KP. A study of factors
    report with quantitative propofol analysis. Anesth Analg 1995;                    concerned in emesis during spinal anaesthesia. Br J Anaesth
    80: 636-637.                                                                      1972; 44: 1208-1211.
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    Acta Anaesthesiol Scand 1994; 32: 95-8.                                           receptor of NIE-115 neuroblastoma cells. Naimya Schmiedeberg’s
8. Ostman PL, Faure E, Glosten B, Kemen M, Robert MK,                                 Archives of Pharmacology 1993; 347: 125-32.
    Bedwell S. Is the antiemetic effect of the emulsion formulation               16. Hammas B, Hvarfner A, Thorn SE, Wattwil M. Effects of
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                                      APPLIED PHYSIOLOGY
                         IMPORTANCE OF POISEUILLE’S LAW FOR ANAESTHESIOLOGIST
              Poiseuille’s law describes the flow of gas through a tube. The law has many applications in pulmonary physiology, notably in so far
     as it applies to laminar flow of gas through the conducing airways. It is also used in pneumotachography to relate flow and pressure changes
     within a tube. The law is stated thus:
                                                                               Where:
                                                                               DP = Change in pressure from one end of the tube to the other
                                    V8nl
                        DP =                                                   V = Flow through the tube
                                    pr4                                        n = Coefficient of viscosity of the gas
                                                                             1    = Length of the tube
                               DP             8n1
                                       =                                     r    = Radius of the tube
                               V               pr4
                                                                             The equation can be rearranged thus:

         Here, the ratio of the pressure difference at the ends of the tube (DP) and the flow through the tube (V), which defines resistance,
     is equated to the remaining variables, notably the length and radius of the tube. The resistance varies directly with the length of the
     conducting tube and inversely with the 4th power of the radius. A two fold increase in the length of the tube doubles the resistance, whereas a
     reduction of the radius by half increases the pressure differential 16 times. In the airways, abnormal narrowing by mucous secretions of other
     lesions can cause significant increases in airway resistance. Poiseuille’s law holds true for any round tube in which laminar flow is
     possible, and pneumotachography is based directly on this law. Because the length and radius of a pressure differential flow sensor remain
     constant and the viscosity of respiratory gases varies only slightly, all of the variables in Poiseuille’s equation can be reduced to a constant
     except DP and V. By rearranging:

               V =        DP                  Where KR = A resistance constant based primarily on the length and radius of the tube.
                          KR
            Using this equation, all that is necessary to measure the V is a means of determining the pressure differential; this is easily accomplished
     by means of pressure transducers.
     Prof. Dr. M. Chandrasekhar
     Prof. & HOD, Dept. of Physiology, Thoothukudy Medical College, Thoothukudy (T.N.)

				
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