Total Intravenous Anesthesia for Patients with Chronic Renal Failure

With Propofol and Remifentanil.

By Eduardo Morales, MD August 2010

CONTENTS
Background Preoperative Assessment Monitoring the patient Total intravenous technique Muscle relaxation Postoperative analgesia with fentanyl Fluid management Scientific support

Background
Since life expectancy has increased, we are currently faced with the task of performing anesthesia management for more complicated patients every day. Renal failure is one of these pathologies that we see more frequently. Anesthesia for these patients has many implications. There are some questions that we have to clarify as part of the preoperative assessment.

Preoperative assessment
1. What is the severity of the CRF? This will be determined by the creatinine clearance value or by the glomerular filtration rate (GFR). Patients having less than 10 ml of GFR are experiencing severe renal failure. Those between 10 and 50 ml are in moderate renal failure.

2. What is the aetiology of the CRF? There are many reasons for a patient developing chronic renal failure. Some of the most common causes or co morbidities associated with CRF are: Diabetes mellitus Blood systemic hypertension Chronic hemodynamic instability (e.g. cardiomyopathies, under treated atrial fibrillation) Gout Vascular disease (e.g. Systemic erythematous lupus) Renal tumours Aging process (usually starting after 75 years of age) 3. What is the type of renal failure in regards to urine production and detoxifying? Oliguric (impaired filtration). Impairment for detoxifying (tubular excretion). Normal or high urinary output (decreased tubular concentration). Ask the patient about the amount of daily urine volume. If the patient is unable to produce adequate urine amount this is a warning in regards to fluid management (avoid volume overload since fluid clearance is impaired). If the patient is able to produce urine but is not detoxifying, the concern would be accumulating metabolites of medications, as well as PH and electrolyte imbalance. If the urinary output is high (rare, e.g. nephrotic syndrome), the risk is hypovolemia. 4. What is the potassium level? (Higher levels than 7 mEq/L are related to dangerous cardiac arrhythmias). This patient must be dialyzed before elective surgery. 5. Are the uremic levels too high? If the patient is not receiving adequate treatment for uraemia (dialysis), the creatinine levels can be very high; there can also be electrolyte imbalance, acidbase disorders and organ dysfunction, mainly manifested by hyperventilation, myocardial contractility dysfunction and neurological dysfunction (lethargy, disorientation). 6. Are there any other indications for dialysis? For instance: congestive heart failure, pericardial tamponade, uremic platelet dysfunction. 7. Are there any signs of hypervolemia (e.g. crackles, chest tightness, laborious respiratory work, external jugular vein distension with 45 degrees head up supine position). 8. Are there any signs of hypovolemia (e.g. collapsed peripheral veins, thirst, nail bed vasoconstriction; weak, empty, rapid pulse). 9. Arterial blood gas analysis (ABG) will provide important information to assess acid-base balance. 10. EKG may show ventricular hypertrophy, ischemic changes, conduction delays and T wave elevation from hyperkalemia. 11. Echocardiogram will provide you with accurate, valuable, cardiac function information (ventricular E.F, diastolic dysfunction).

Monitoring the patient

The extent of monitoring depends on the type of surgery and the estimated surgical time. The longer or complicated the procedure is, the more detailed and complex the monitoring should be.

CVP: For longer procedures or for those that we expect a significant fluid shift or bleeding. Monitoring CVP is mandatory in these cases, in order to avoid either fluid overload or insufficient volume supply during the surgery, as well as guidance for postoperative fluid requirements. If the procedure is short or doesnt involve a significant fluid loss (e.g. timpanoplasty, hernia repair, laparoscopic cholecystectomy), we can monitor for ingurgitation of external carotid vein for estimation regarding fluid overload. Blood pressure: invasive monitoring (arterial line) is required if there is suspicion of hemodynamic instability or if several arterial blood samples are needed (ABGs). For all other patients, NIBP monitoring is enough. Temperature monitoring: is important since these patients are sensitive to dropping temperature due to autonomic dysfunction. Measures to preserve temperature should be encouraged. Urinary catheterization is important to monitor urinary output. Infection of the bladder may also be present. Muscle relaxation monitoring is important if you need to provide relaxation throughout the surgery (e.g. intra abdominal procedures). ETCO2, SPO2 and EKG (5 leads) are monitored as we routinely do.

Anesthesia Technique
General Considerations
If the patient is receiving dialysis, note the last time it was given. Usually, being hemodialyzed 24 hrs prior to surgery is appropriate. Peritoneal dialysis may be performed even the same day, pre and post operatively. It is always better to transfuse the patient during haemodialysis if the haemoglobin levels have to be optimized preoperatively. Note the presence of A-V shunts before attempting any vascular access and avoid proximity between both, in order to prevent infections or phlebitis. Correct clotting problems by adjusting anticoagulants or supplying Fresh Frozen Plasma (FFP) before surgery. Consider the A-V shunt integrity when positioning the patient. Prevent direct pressure or vascular compression to the area. Since safety is the number one concern in anesthesia, consider the options before using a Laryngeal Mask Airway (LMA); the possibility of gastric aspiration is higher in renal failure patients and the endotracheal tube is always the golden standard for airway protection. Regional anesthesia may not be the best choice since clotting problems may be present. There is also a higher incidence of neuropathies associated with renal failure and liability problems may arise.

Total Intravenous Anesthesia with propofol remifentanil (TIVAp-r)

Why TIVAp-r? Its a safe approach since the development of drugs (remifentanil, atracurium, cysatracurium), which are non organ metabolized, and also from those that are metabolized and excreted by organs other than the kidneys (propofol). TIVA is a non-toxic technique, very stable from the hemodynamic point of view. Fluoride volatile general anaesthetics have been associated with renal damage. If postoperatively, renal function decreases, the volatile anesthetic can be blamed for this; thus, also for liability purposes, TIVA is safer. In fact, an easy technique for TIVA is described as follows: Induction: is made with propofol at the regular dosage (1.5 to 2.5 mg/kg) expected for a patient with no renal failure. Maintenance: The pharmacokinetic profile of propofol after infusion is not markedly affected by renal failure; however, CRF patients may wake up faster after discontinuing the propofol infusion, compared to patient with normal renal function. Clearance of propofol is predominantly metabolic. Little or no unchanged propofol is detected in excreta; this emphasizes the importance of the liver clearance of propofol. There is no difference in the pharmacokinetic profile of propofol in uremic patients requiring haemodialysis compared to healthy patients. Maintenance is performed with a mix of a propofol 1% solution (non diluted, 10 mg per ml) in a 50 ml syringe (500 mg of propofol) and the addition of remifentanil 1 mg to the same syringe. This mix will provide a solution with a ratio of Propofol: Remifentanil of 500:1. The dosage at the infusion calculator (syringe driver, syringe infuser or syringe infusion pump) should be set up as a maintenance ranging from 100 to 125 mcg/kg/min of propofol. Start the infusion at the same time as the induction. See table 1.

Propofol (mcg/kg/min) Remifentanil dosage (mcg/kg/min) 75 ............................................. 0.15 90 .............................................. 0.18 100 .............................................. 0.20 110 .............................................. 0.22 120 ........................................... 0.24 125 ........................................... 0.25 Table 1. Dosage of Propofol : Remifentanil (500:1), based upon the propofol infusion rate. As remifentanil is an agent that induces bradycardia, this effect has to be counteracted in order to maintain hemodynamic stability and a normal cardiac output (using either atropine or glycopyrrolate). Any sign of light levels of anesthesia should be treated with small propofol boluses (e.g. 50 mg) until the desired level has been reached. The patient usually wakes up 8 to 10 minutes after the infusion has been stopped.

Narcotic management: since remifentanil is the drug of choice during the maintenance of TIVA in
patients with renal failure, the only consideration on this regard would be that metabolizing time for remifentanil is slightly prolonged. Patients will have good breathing control after 15 minutes of discontinuing remifentanil and no effect after 20 minutes (in comparison to 8 minutes for breathing control and 12 to 15 minutes for no remaining effect on healthy patients).

Muscle relaxation
The best approach for muscle relaxation would be the benzyl isoquinoline (atracurium, cys atracurium) group of NMBA (neuromuscular blocking agents), because they are metabolized by non specific esterases of plasma and tissues, and by reaching body temperature and plasmatic PH. Intubation can be accomplished either with any non depolarizer NMBA (e.g. small dose of rocuronium (20 mg for an adult) if shorter intubation times are preferred) or with succinylcholine, provided normal potassium levels, and then continue with cys-atracurium; or start with the latter and wait 90 seconds for intubating conditions. Atracurium at larger doses than 0.4 mg/kg can be associated to arterial hypotension from histamine release and vasodilatation, which is transitory (aprox. 5 minutes). A single dose of a vasopressor agent can be used in such cases.

Postoperative analgesia with fentanyl

In regards to postoperative pain management, intravenous fentanyl analgesia is the first choice. In narcotic nave patients: Table 2 Fentanyl IV dose 5 mcg/kg 5 - 10 mcg/kg 10 20 mcg/kg

Surgical time up to 1 hour 1 2 hrs > 2 hrs

(e.g. colectomy, gastrectomy, femur shaft ORIF) This dose can be given at the beginning of the surgery (during the incision, if the patient is hemodynamically stable) either in several IV pushes or in a small volume infusion. The larger fentanyl doses can cover up to 4 to 6 hours of postoperative pain. A fentanyl PCA pump can be used for longer pain management. Postoperative supplemental oxygen is necessary (e.g. nasal prongs 3 LPM) in order to avoid hypoxemia on the ward, any time that a narcotic PCA is being used.

Fluid management
The most efficient way to protect the kidneys during surgery is ensuring an adequate intravascular volume, maintain cardiac output and avoid drugs known to decrease renal perfusion. Fluid management in end stage (severe) renal failure: Normal saline solution is a safe approach. Careful measures must be taken with Ringers Lactate because of the content of potassium and lactate (acid) component, and its slight hypo osmolality (273 mOsm/L). For volume expansion, careful administration of a hetastarch solution (e.g. Voluven, Pentaspan) can be considered, since it remains intravascularly for six hours, and can improve the microcirculation (compared to crystalloid solutions that are only expected to remain intravascularly for 20 or 30 minutes). Another important hemodynamic feature in CRF patients is their usually low albumin level, which complicates the microcirculatory dynamic due to a low capillary oncotic pressure. Severe anaemia has to be avoided. Even though patients with CRF are known for managing properly haemoglobin levels consistent with anemia, special care has to be taken in order to avoid ischemia in patients with Ischemic Heart Disease (e.g. coronary artery disease, aortic stenosis) or cerebro vascular disease (previous episodes of stroke, TIA). Observe intermittently your EKG monitor for ST segment depression. Any value lower than minus 2 mm (-2 mm) must be treated to lower the risk of ischemic episodes intra or postoperatively. One of the measures of treatment is maintaining adequate haemoglobin levels in order to keep the myocardium well oxygenated. Keeping a tight control on fluid loss (bleeding), CVP is mandatory in longer or more complex procedures. Higher CVP values can be necessary to keep adequate left ventricular end diastolic volume (cardiac output) in patients with diastolic dysfunction since their ventricle is thicker and stiffer (e.g. arterial hypertension, obesity, diabetes mellitus, ischemic heart disease, hypertrophic cardiomyopathy).

Fluid management in kidney dysfunction (moderate renal failure)

This group of patients is the most common. We can assume that a decrease in renal function reserve may involve most of the patients older than 75 years of age. Renal function is moderately decreased anywhere from 10 to 45%. They have impairment of fluid distribution (due to a low cardiac output) and may not tolerate well the surgical challenge. Risk factors for further deterioration of renal function are usually related to a low cardiac output syndrome (e.g. hypovolemia, atrial fibrillation, sepsis or severe systemic inflammatory response syndrome); drug toxicity, which may include most commonly, ACEIs, NSAIDs and aminoglycoside antibiotics amongst others; and of course, inadequate fluid management. CVP monitoring is mandatory in larger procedures in order to have proper cardiac filling pressures and tight maintenance of fluid supply. Generous hydration is advised since the consequences of excessive fluid overload (pulmonary congestion or edema) are easier to treat than acute renal failure.

In these patients, the use of inotropes may be indicated. A low dose infusion of dopamine or dobutamine (e.g. 3 mcg/kg/min) is a very useful measure in patients with moderate to severe vascular damage, since these drugs provide a better perfusion pressure to vital organs (cerebrovascular disease, history of TIA or stroke). Small, intermittent doses of vasopressors (e.g. ephedrine, phenylephrine) can be given also to maintain desirable blood pressure levels, but those that are exclusively alpha 1 agonists (e.g. phenylephrine) may decrease cardiac output if given repeatedly. In most cases the patient will need a small dose of furosemide (10-20 mg IV). Mannitol 20% (0.5 grs/kg) can be given instead of loop diuretics and can be more useful in order to bring interstitial fluids back into the intravascular compartment in the presence of hypoalbuminemia, due to its high osmotic pressure.

Scientific support:
1. Propofol infusion for induction and maintenance of anesthesia in patients with end-stage renal disease. British Journal of Anaesthesia 1998: 81: 845-860. 2. Pharmacokinetics and Pharmacodynamics of propofol infusions during general anesthesia. Anesthesiology 1988: 69: 348-356. 3. Effect of renal failure on drug metabolism by the liver. British Journal of anesthesia 1993: 71: 282-290. 4. Renal function and anesthesia. Anesthesia Secrets. 2006: 294-301.