Evaluation of the Effect of Two Types of Fluid in the Recovery From Anaesthesia. Voluven 6% v Hartmanns
Condition: Postoperative Nausea and Vomiting
MeSH terms: Vomiting; Postoperative Nausea and Vomiting
Study type: Interventional
Phase: Phase 3

Summary: 
      Avoiding nausea and vomiting is one of the most important for patient comfort and
      satisfaction, and preventing unplanned overnight stays in hospital following surgery. Studies
      have shown that increased amounts of intravenous fluid during surgery prevent nausea and
      vomiting after operations. This effect lasted for up to 48 hours after the surgery. Other
      unpleasant side effects of dehydration that delay recovery including headaches and dizziness
      can be prevented with fluid treatment during the operation. It is unclear if this effect
      happens with all types of fluid. The investigators propose to examine the effect of 2 types
      of intravenous fluids on recovery from anaesthesia. Each group will be given a different
      fluid while using our usual anaesthetic technique. The investigators will ask questions about
      nausea and vomiting after surgery (primary outcomes), and other factors relating to patient
      comfort such as headache and dizziness (secondary outcomes)
    

Detailed description: 
      Treatment of postoperative nausea and vomiting (PONV) is extremely important for patient
      comfort and satisfaction after surgery.1 There has been a recent change in emphasis from
      inpatient to day care surgery and anaesthesia with attendant increased interest in the
      problem of PONV. The incidence of PONV following day case gynaecologic surgery is 40% to
      90%.2,3 Postoperative nausea and vomiting has the potential to cause delays in meeting
      discharge criteria both from the recovery room to ward, and from the day ward to home. On
      rare occasions, it may lead to unanticipated overnight hospital admission which leads to an
      increased emotional cost to the patient and economic cost to the healthcare provider. The
      efficacy of routine use of prophylactic antiemetics remains controversial.4 Pharmacologic
      prophylaxis has limited effect and increases the risk of adverse drug effects for the patient
      in addition to increasing overall cost of care.5,6

      Studies suggest that increased crystalloid infusion for day case gynaecologic procedures in
      healthy patients reduces the incidence of nausea, vomiting and antiemetic use.7,8 The
      suggested mechanism is an improvement in gastrointestinal mucosal perfusion that mitigates
      the both the deleterious effects of preoperative fasting and consequent dehydration,9 and
      those of raised intra-abdominal pressure and surgical manipulation of bowel during
      laparoscopic procedures. However, excessive fluid administration in major surgery has been
      shown to have a negative effect on postoperative gastrointestinal function (causing an
      increased incidence of postoperative ileus) due to bowel oedema.10 It has been demonstrated
      that colloid causes less bowel oedema than equivalent volumes of crystalloid.11 Moretti et al
      showed that intraoperative colloid administration reduces PONV and improves the quality of
      postoperative recovery versus crystalloid solutions.¹² Clearly, there is an optimum
      perioperative fluid balance to reduce PONV without the risk of additional gastrointestinal
      side effects.

      An arbitrary perioperative fluid load measured in ml.kg-1 does not take account of the
      individual fasting period and resultant preoperative fluid deficit for each patient, which
      can vary substantially depending on early or late (morning or afternoon) operating time.

      We propose to prospectively examine the effect of intravenous fluids on PONV in a
      double-blind study, utilizing a standardised anaesthetic technique as normally carried out in
      this hospital. We hypothesise that replacement of preoperative fluid deficit with colloid
      will reduce the incidence of PONV versus crystalloid solution. We further propose to examine
      secondary outcomes relating to patient wellbeing such as headache and dizziness which are
      symptoms of dehydration.

      Healthy patients should not experience any cardiorespiratory effects associated with
      administration of intravenous fluids to correct dehydration due to preoperative fasting.
      There may however be subclinical effects which can be detected by sensitive pulmonary
      function testing. Patients will be asked to perform a simple bedside lung function test
      before surgery and 2 hours after surgery. This will be done with a portable spirometer
      (Micromedical Micro Lab Spirometer), which is used routinely in our anaesthesia preoperative
      assessment clinic to evaluate lung function. Forced expiratory volume in the first second
      (litre) (FEV1), forced vital capacity (litre) (FVC) and peak flow rates (l/min) will be
      measured at a 45 degree position of recumbency. The best of three attempts will be chosen for
      further analysis as recommended by the British Thoracic Society.

      Methods

      LOCATION · Rotunda Hospital, operating theatres, recovery room and gynaecology ward

      STUDY DESIGN

      · Prospective, randomised, double-blind

      INCLUSION CRITERIA

        -  ASA I-II female patients

        -  Age 18-45 years

        -  Undergoing minor elective gynaecological surgery (elective laparoscopy)

      EXCLUSION CRITERIA

        -  Age <18 or > 45

        -  Cardio-respiratory disease

        -  Excessive intraoperative blood loss

        -  Obesity: BMI >30

        -  Relevant drug allergy to medication used in the protocol

      INFORMED WRITTEN CONSENT · Informed written consent will be obtained from all patients (see
      appendix 1)

      RANDOMISATION

      · Patient group will be determined by randomisation with a computer program random number
      generator

      GROUPS

        -  Patients will be allocated to one of two groups according to randomisation

        -  Group 1 will receive 1.5 ml.kg.hr-1 of fasting time of intravenous Hartmann's solution
           perioperatively (Crystalloid solution)

        -  Group 2 will receive 1.5 ml.kg.hr-1 of fasting time of intravenous Voluven® (6% Hydroxy
           Ethyl Starch) solution perioperatively (Colloid solution)

      BLINDING

        -  All fluid administration will be completed in theatre

        -  Neither the patient or the investigator will be aware of group assignment

      ANAESTHETIC TECHNIQUE The anaesthetic technique will be standardised as follows: Intravenous
      access will be obtained after local anaesthetic infiltration of the skin. Once the fluid has
      been started all patients will undergo a standardised induction of anaesthesia, consisting of
      Fentanyl 1.5 mcg.kg-1, Propofol 2-3 mg.kg-1 and Atracurium 0.35 mg.kg-1 to facilitate airway
      control. All patients will be mechanically ventilated via a laryngeal mask airway LMA
      Supreme™ to maintain isocapnia with tidal volume (Vt) 4-6 ml.kg-1, maximum airway pressure (P
      max) 30 cm H2O and a positive end expiratory pressure (PEEP) of 5 cm H2O. Anaesthesia will be
      maintained with Sevoflurane 1-3% in a mixture of O2 and air to achieve a FiO2 of 0.5. Muscle
      relaxation will be antagonised with Neostigmine 2.5 mg and Glycopyrrolate 0.5 mg at the end
      of surgery. Before discontinuation of anaesthesia, each patient will receive rectal
      Diclofenac 100mg and 1000mg Paracetamol i.v.

      Postoperative care will also be standardised. Patients complaining of pain will be given 25
      mcg of Fentanyl intravenously as required (in PACU), Pethidine 50mg intramuscularly or simple
      oral analgesics (Paracetamol/Codeine 500-1000mg/8-16mg) every 6 hours in the ward area.
      Rescue antiemetics in the form of boluses of Ondansetron 4mg intravenously (to a maximum
      total dose of 16mg) and Cyclizine 50mg intramuscularly every 8 hours can be given. Patients
      will be prescribed oral Paracetamol/Codeine 500-1000mg/8-16mg every 6 hours and Diclofenac
      50mg every 8 hours to take at home if required.

      MEASUREMENTS (assessed by a single data collector @ 30 mins, 2 hours, 24 hours and 48 hours
      postoperatively)

        1. Nausea: using a standard verbal analogue scale (VAS 0 - 10)

        2. Vomiting: Y/N, number of episodes

        3. Rescue antiemetics administered

        4. Dizziness: Y/N

        5. Sore throat: Y/N

        6. Headache: Y/N

        7. Wellbeing: assessment of general wellbeing on a scale from 0 - 10

        8. Pulmonary Function Tests

      TREATMENT OF DATA The data will be collected by a single investigator at the specified time
      points and documented on a patient data collection sheet (see appendix 2). Once data
      collection is complete, all data of the patient sheets will be transferred onto a spreadsheet
      and anonymised.

      USE OF DATA The data will be presented at a national or international meeting and in
      peer-reviewed medical journals.

      STORAGE OF DATA All data will be stored for five years and only Dr. Conan McCaul and Dr. Ivan
      Hayes will have access to them.

      STATISTICAL PROCEDURES Statistics will be performed using a standard statistical program
      (Sigma Stat, Jandel Scientific). Demographic data will be analysed using Student's t-test or
      Fisher's exact test as appropriate. Repeated measures ( VAS scores) will be analysed by
      repeated measures analysis of variance with further paired comparisons at each time interval
      performed using the t-test, with corrections for multiple comparisons where appropriate.
      Categorical data will be analysed using χ² analysis or the Fisher's exact test where
      applicable. Normally distributed data will be presented as means +/-SEM, non-normally
      distributed data will be presented as medians +/- quartiles (interquartile range), and
      categorical data will be presented as raw data and as frequencies.

      SAMPLE SIZE Postoperative nausea and vomiting incidence from day case laparoscopic
      gynaecologic procedures (primary outcome) both with and without single agent antiemetic
      prophylaxis varies from 40 -90%.2,3,7 To detect a clinically significant difference of 25%
      reduction in mean nausea scores based on a PONV incidence of 40% without antiemetic
      prophylaxis, we calculate a sample size of 60 patients per group (a = 0.05, β = 0.2).
    

Intervention name(s): fluid administration
Intervention type(s): Other
Intervention description(s): 1.5mls/kg/hr fasting
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Perioperative intravenous fluids