Liberal Versus Restrictive Fluid Protocols in Adults
Condition: Intraoperative Complications
MeSH terms: Intraoperative Complications
Study type: Interventional
Phase: Phase 2

Summary: 
      The term acute kidney injury (AKI) is used to describe a rapid deterioration (hours to days)
      of renal function. This rapid deterioration leads to accumulation of plasma waste products,
      such as urea and creatinine.

      Accumulation of urea and other nitrogen-containing substances in the blood stream lead to a
      number of symptoms, such as fatigue, loss of appetite, headache, nausea and vomiting. Marked
      increases in the potassium level can lead to irregularities in the heartbeat, which can be
      severe and life-threatening. Fluid balance is frequently affected, though blood pressure can
      be high, low or normal. Pain in the flanks may be encountered in some conditions (such as
      thrombosis of the renal blood vessels or inflammation of the kidney); this is the result of
      stretching of the fibrous tissue capsule surrounding the kidney.

      Perioperative AKI is a leading cause of morbidity and mortality; It is associated with
      increased risk of sepsis, anemia, coagulopathy, and mechanical ventilation.

      The first publication of consensus criteria for AKI was published in 2004. The system was
      named RIFLE (risk, injury, failure, loss of kidney function and end-stage renal failure) and
      used sCr or urine output to define AKI.

      Later, in 2007, a modified definition of the RIFLE criteria was published by the Acute Kidney
      Injury Network (AKIN) .Although the AKIN criteria evolved from the RIFLE criteria, a major
      advance was the understanding that even small changes in sCr concentrations are associated
      with increased morbidity and mortality. The AKIN criteria allowed definition of AKI even
      without knowledge of baseline sCr.

      In 2012, a clinical practice guideline of AKI was proposed by the Kidney Disease Improving
      Global Outcomes (KDIGO) Foundation. The guideline included a comprehensive review of AKI
      definition, risk assessment, diagnosis, prevention, treatment and renal replacement therapy.

      A common practice to maintain effective blood volume and thus kidney perfusion is intravenous
      (I.V.) hydration. Correcting hypovolemia is an essential perioperative hemodynamic goal and
      appropriate hydration is considered important for the avoidance of AKI.

      Perioperative fluid therapy has been studied extensively, but the optimal strategy remains
      controversial and uncertain. Much of the current debate surrounds the type of fluids
      administered (colloid versus crystalloid), the total volume administered (restrictive versus
      liberal), and whether the administration of fluids should be guided by hemodynamic goals
      (goal directed [GD] versus not goal directed).

      Administering a large amount of I.V. fluid in the perioperative period is a common clinical
      practice. Although fluid loading may expand intravascular space, improve organ perfusion or
      tissue oxygenation and reduce minor postoperative complications in laparoscopic surgery,
      excessive fluid may also increase some perioperative complications.

      Intraoperative urine output is often monitored but rarely responds to fluid administration.
      Clearance of fluid during general anesthesia is only a small fraction of that observed in
      conscious volunteers. Infusion of crystalloids during anesthesia shows reduced clearance and
      slower distribution such that intraoperative oliguria may not reflect fluid status or predict
      future AKI.

      Given that liberal fluid administration can be correlated with worse postoperative outcome,
      the recommendation to maintain urine output of at least 0.5 ml/kg/h should be considered.
    

Detailed description: 
      Prior to surgery, all patients will undergo pre-anesthetic checkup including detailed
      history, physical, systemic examination, height and weight of the patient. All patients will
      be investigated for exclusion of any of the above mentioned contraindications. Routine
      preoperative laboratory investigations as complete blood count, grouping, coagulation
      profile, electrolytes and preoperative baseline serum creatinine will be measured. Patients
      should have low molecular weight heparin administered till the evening prior to daytime
      trauma lists. This precaution allows for an appropriate window of time to minimize the risk
      of bleeding related to neuraxial anesthesia. All patients will be kept nil per mouth 6 h for
      solids and 2 h for water and clear liquids.

      Preparation of the patient and conduct of anesthesia:

      Written consent and emergency resuscitation equipments including airway devices, advanced
      life support drugs for LA toxicity and intraoperative adverse events will be available. All
      patients will be anesthetized by the same team of anesthesiologists and operated upon by the
      same surgeon who will be unaware of the study medications.

      After arriving at the operative room, the pulse oximetry, electrocardiography, temperature
      probe and non-invasive blood pressure monitor will be applied. A large bore I.V. cannula (18
      gauge) will be inserted.

      Spinal anesthesia will be used for all patients. Under aseptic technique and local skin
      infiltration with 1% lidocaine, spinal anesthesia will be performed at the L3-4 or L4-5
      spinal interspace by 25 gauge spinal needle. After successful cerebrospinal fluid
      recognition, 10 mg heavy bupivacaine 0.5% mixed with 25 ug fentanyl will be injected into the
      subarachnoid space. Then the spinal needle will be removed and the patients will be
      positioned carefully to the suitable position. Once adequate anesthesia to at least T10
      dermatome achieved, the operation will be allowed to be started. Supplemental oxygen will be
      administered via face mask at flow rate between 5 and 8 L/min. Management of the patients
      will be performed by another anesthesiologist unaware about the used protocol. Vital signs
      including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP),
      mean blood pressur (MBP) and arterial oxygen saturation (SpO2) will be recorded as baseline 5
      min before conduction of spinal anesthesia, immediately after conduction of anesthesia then
      every 5 min till end of surgery. The level of sensory block will be assessed before beginning
      of surgery using an ice cube. Urinary catheter will be inserted for all patients. Hypotension
      defined as decrease in mean blood pressure (MAP) to more than 20% of baseline values will be
      treated with a 3 mg I.V. bolus of ephedrine repeated every 2 min if hypotension persists. If
      hypotension persists after 30 mg ephedrine, additional amounts of Ringer's lactate (5ml/ kg)
      will be infused through the 18 gauge cannula.

      Patients will be asked to report any intraoperative pain or discomfort using visual analog
      scale (VAS) of 0-10.

      After finishing surgery, patients will be transferred to the surgical ICU where they will be
      monitored by an intensivist who will be blinded to the study group.

      Once the patients sent to ICU, both groups will receive 1.5 ml/kg/h of Ringer's lactate
      solution as fluid maintenance. Follow-up will be done for 5 days postoperatively using:

        -  Monitors for HR, SBP, DBP, MBP, SpO2 , respiratory rate and recovery time of motor
           blockade (up to Bromage 2)

        -  Analgesia: paracetamol 1 gm/ 6 hours regularly

        -  Supplemental oxygen will be provided in the first 24 hours after the operation if
           arterial oxygen saturation < 94%.

        -  Early mobilization: will improve oxygenation and respiratory function.

        -  Fluid balance as hypovolemia is common postoperatively and oral fluid intake should be
           encouraged over the intravenous route.

        -  Urinary tract infections (UTI): is common and urinary catheters should be removed as
           soon as possible to reduce the risk of infection and urine output will be collected and
           calculated as [after 12 hours, on day 2 (in 24 hours), 3 (in 24 hours), and 5 (in 24
           hours after surgery]

        -  Routine laboratory investigations as CBC, coagulation profile, electrolytes, blood urea
           and serum creatinine.

        -  Symptoms suggestive of AKI: fatigue, loss of appetite, headache, nausea, vomiting and
           pain in the flanks Patients will be discharged from ICU when hemodynamics are stable and
           laboratory investigations are within normal.
    

Intervention name(s): Ringer lactate
Intervention type(s): Drug
Intervention description(s): Randomization will be done using computer generated table of random numbers in a 1:1 ratio and will be conducted using sequentially numbered, opaque and sealed envelope. The trial will be planned that neither the doctors (investigators) nor the patients will be aware of the group allocation and amount of fluid received. Intraoperative and postoperative data collections will be achieved by the same blinded anesthiologist.
Patients will be randomly allocated into two groups:
Group L: 40 patients who will be subjected to ''liberal" approach of intraoperative 18-20 ml/kg/h of Ringer's lactate starting from conduction of spinal anesthesia.
Group R: 40 patients who will be subjected to ''restrictive" approach of intraoperative 4-6 ml/kg/h of Ringer's lactate starting from conduction of spinal anesthesia.
Blood loss will be replaced if more than 500 ml in a ratio of 3 ml crystalloid: 1 ml blood.
Other intervention name(s): lactated ringers solution
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: comparing the effect of two different protocols of fluid therapy (liberal versus restrictive) in adult patients undergoing unilateral orthopedic lower limb surgery under spinal anesthesia
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: liberal, restrictive, fluid, RIFLE