RENAL DiSEASE AND ANESTHESiA
Typical preoperative diagnostic testing in patients with chronic kidney disease
Anesthesia concerns for a patient with CKD
Preoperative assessment
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Patient’s body weight is to be recorded
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Muscle mass is reduced
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Weight trend gives an idea regarding volume status
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Venous access may be difficult
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Care of AV fistula
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Do not inject drugs into it nor IV fluid infusion
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Do not apply the cuff to measure blood pressure
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Should be well-padded with gauze
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Last hemodialysis session
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Patient may be hypovolemic if he has undergone dialysis a few hours prior to surgery with increased risk of hypotension with induction of anesthesia
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If hemodialysis is due in the immediate future, patient may be overhydrated, with increased risk of pulmonary edema in the perioperative period
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Delayed gastric emptying
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Rapid sequence induction in uremic patients
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Gastric acidity
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Increased risk and severity of aspiration pneumonia
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Preoperative intervention/optimisation
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Preop Optimisation plan
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Control of hypertension
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Correction of coagulopathy
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Correction of hyperkalemia
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Preoperative hemodialysis
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Correction of anemia
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Premedication
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Should be kept to a minimum (increased susceptibilty to sedation and respiratory depression)
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Morphine/meperidine — avoided
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Short acting anxiolytic (e.g. midazolam) may be used
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Glycopyrrolate is preferred to atropine and scopolamine (to minimise CNS effects)
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Ranitidine—Reduced dose (primarily excreted through kidneys)
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Sodium bicitrate—Before emergency cases
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Avoid cimetidine (inhibits Cyt P50; increases duration of action of many drugs)
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Inside the operating room
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Immunosuppression
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Strict asepsis is imperative
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Broad spectrum antibiotic coverage needed prior to surgery
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Cyclosporine—prolong neuromuscular blockade
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Increased risk of hepatitis and HIV in dialyzed patients
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Anesthesia staff should wear gloves at all times and goggles during airway manipulation.
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Careful positioning
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Renal osteodystrophy (fragile bone and joints)
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Skin integrity diminished (susceptible to pressure related injuries)
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Sensory neuropathy
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Prepare for hemodynamic fluctuations
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Most patients may be having refractory hypertension / fluid depleted / fluid overloaded
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High risk of pressor response during laryngoscopy
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Hemodynamic instability following neuraxial blockade
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Choice of drugs/dosage adjustments/nephrotoxicity
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Measures to prevent acute kidney injury
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Hypothermia—prevention measures
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Increase ambient temperature in the operating room (OR)
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Heater-humidifier to warm and moisten inspired gases
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Forced-air convection blanket
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IV fluid warmers
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During emergence in CKD patients
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Delayed recovery
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Hypertension
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Respiratory depression
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Pulmonary edema
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Vomiting and aspiration
Preoperative Preparation Strategies
The main strategies for preoperative preparation of patients with CKD for elective surgery are:
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Control of hypertension
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Correction of coagulopathy
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Correction of hyperkalemia
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Preoperative hemodialysis
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Correction of anemia
a) Control of Hypertension
Control of hypertension can be achieved with salt and water restriction, weight loss if indicated, and pharmacologic therapy. The ability of the kidney to adjust to variations in sodium and water intake becomes limited as renal failure progresses. An elevated sodium chloride intake leads to congestive heart failure, edema, and hypertension, whereas
low salt intake leads to volume contraction and hypotension. A mildly decreased salt diet (4 g/d) can be started, and salt intake should be reduced to 2 g/d if hypertension persists. Initial drug therapy can include ACE inhibitors or angiotensin II receptor blockers (if serum potassium and GFR permit), calcium channel-blocking agents, diuretics, and β-blocking agents. The adjunctive drugs that are often needed (e.g. clonidine, hydralazine, minoxidil) reflect the difficulty of achieving and maintaining hypertensive control in these patients.
The joint recommendations of the American Society of Nephrology and the National Kidney Foundation provide useful guidelines for management of hypertensive patients with CKD. They recommend a goal BP for all CKD patients of <130/80 mm Hg and the need for more than one antihypertensive drug to achieve this goal. The guidelines indicate that most patients with CKD should receive an Angiotensin-converting enzyme inhibitors (ACEI) or an Angiotensin II receptor blockers (ARB) in combination with a diuretic, and many will require a loop diuretic rather than a thiazide. In CKD patients with diabetes or proteinuria > 1 g per 24 hour, blood pressure should be reduced to 125/75 mm Hg, if achievable without prohibitive adverse effects. In addition, if there is a conflict between the goals of slowing progression of CKD and CVD risk reduction, individual decision making is recommended based on risk stratification.
Proceeding with elective surgery may be acceptable in presence of chronic moderate hypertension. Severe or labile hypertension, especially if symptomatic (e.g. angina, headache, nausea, visual deterioration), must be controlled in the preoperative period.
(b) Correction of Coagulopathy
Treatment is required only in patients who are symptomatic. The options include:
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Raising the hematocrit to 30% can reduce bleeding time
in many patients.
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Desmopressin (1-desamino-8-D-arginine vasopressin;
DDAVP)
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Dose: 0.3 mcg/kg intravenously; infused over 15–20 minutes (rapid infusion can cause acute hypotension
due to vasodilatation)
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Causes release of factor VIII bound to von Willebrand’s factor from endothelial cells
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Onset: 1–2 hours; Duration of action: 6–12 hours
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Most appropriate time to infuse DDAVP would be about1 hour before surgery or anticipated blood loss
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Repeated DDAVP can cause tachyphylaxis due to depletion of endothelial stores of vWF-VIII complex. It may require 4–7 days to restore response to DDAVP
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Conjugated estrogens 0.6 mg/kg diluted in 50 ml of normal saline infused over 30–40 minutes daily, or 2.5–5 mg orally for 5–7 days, have an effect for several weeks.
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Dialysis improves the bleeding time but does not normalize it. Peritoneal dialysis is preferable to hemodialysis because the latter requires heparin to prevent clotting in the dialyzer.
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Cryoprecipitate (10–15 bags) is rarely used and lasts less than 24 hours. (Each cryoprecipitate provides a 1—donor exposure to the receipient and increased risk of blood borne infection).
(c) Correction of Hyperkalemia
Hyperkalemia is a major risk in patients who present for emergency surgery with sepsis, catabolic stress or acidosis. Treatment should be initiated if K+ >6.5 mmol/liter or ECG changes present. The medication used in acute treatment of hyperkalemia are given in Table below. Unlike hypokalemia, the incidence of serious cardiac compromise is high and therefore intervention is important. Treat the cause if possible.
(d) Preoperative Hemodialysis
Most manifestations of uremia, such as coagulopathy and encephalopathy are controlled if blood urea nitrogen (BUN) is kept <100 mg/dl. Patients on hemodialysis should undergo dialysis during the 24 hours preceding the elective surgery. This will minimise the likelihood of uremic bleeding, pulmonary edema and impaired arterial oxygenation. Depending on the planned surgery, the use of heparin may be avoided or minimised during the preoperative hemodialysis. Appropriate adjustment of intravascular volume can also be achieved.
The goals of preoperative hemodialysis include:
a. Optimise fluid and electrolyte status
b. Reduce BUN <100 mg/dl
c. Facilitate preoperative blood transfusion, when indicated.
Excessive dialysis may induce intravascular hypovolemia (even in the face of peripheral edema) and electrolyte deficits (hypokalemia, hypomagnesemia, hypophosphatemia). It may precipitate decrease in left ventricular ejection fraction and perfusion defects suggestive of myocardial ischemia without acute ECG changes and in the absence of history of coronary artery disease.
In case of ESRD patient who has never been on dialysis, it is unwise to start dialysis immediately prior to surgery. Patient should be treated conservatively. But prepare for possibility of dialysis in early postoperative period (to facilitate removal of sequestrated fluid or for acute hyperkalemia).
For patients undergoing cardiac surgery, dialysis can be provided during cardiopulmonary bypass.
CAPD (Continuous Ambulatory Peritoneal Dialysis) may be continued until the time of surgery and restarted postoperatively only when it can be assured that the patient’s ventilatory status will tolerate the abdominal distension it induces.
(e) Correction of Anemia
Human recombinant erythropoietin (50 to 75 IU/kg subcutaneously triweekly).
Target hemoglobin/hematocrit = 11–12 g/dl; 33–36%
Optimal rate of correction: Rise in hematocrit by 4–6% over 4 week period.
(If patient is iron-deficient, i.e. T sat < 20%; Ferritin < 100 ng/ml—administer iron 50–100mg IV twice per week for 5 weeks. Consider folate supplimentation also.)
Acceptable hematocrit (Hct) levels:
CKD without ischemic heart disease: Hct > 25% CKD with ischemic heart disease: Hct > 30%
If hemoglobin (Hb) is <5 g/dl, preoperative transfusion is recommended (ideally during hemodialysis, as it will take care of the hyperkalemia and volume status. It may be noted that a 3 week old bank blood may contain about 21 mEq/l of potassium).
If Hb = 5–8 g/dl, replace the intraoperative blood loss with packed RBCs.
If Hb is more than 8 g/dl, blood loss of up to 500 ml need not be replaced with transfusion.
Concerns during anesthetic emergence in CKD Patients
The potential problems encountered during emergence are:
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Delayed recovery
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Hypertension
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Respiratory depression
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Pulmonary edema
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Vomiting and aspiration
Patients should not be extubated until they are fully awake, preferably in the lateral position, to reduce the risk of aspiration. If in doubt, a short period of postoperative mechanical ventilation may allow controlled emergence, avoid unnecessary use of reversal agents and afcilitate proper evaluation of neurologic and ventilatory function prior to extubation.
The excretion of all cholinesterase inhibitors is delayed in patients with impaired renal function to the same and perhaps to a slightly greater extent than is the elimination of muscle relaxants. Thus “recurarisation” after reversal of neuromuscular blockade in a patient with renal failure is, in most cases, due to some other causes.
Hypothermia can contribute to delayed emergence. Persistent neuromuscular blockade by increased magnesium may be partially antagonised by calcium.
Postoperative Care
Initial assessment should include:
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Evaluation of airway reflexes
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Volume status: Intake-output (I/O) chart
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Residual neuromuscular (NM) blockade
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Opioid effects
Chronic metabolic acidosis limits the reserve to buffer opioid-induced CO retention. Even the modest degree of 2
hypercarbia may rapidly result in low pH and increased risk of hyperkalemia.
Typical laboratory investigations comprise of: hematocrit, BUN, creatinine, electrolytes, 12-lead ECG (potassium imbalance, intraoperative ischemia), chest X-ray (pulmonary edema).
The recovery room nurse should be informed of the site of an arteriovenous fistula to prevent the blood pressure inadvertently being taken on the same arm. Every attempt should be made to keep the patient warm as shivering, which is common for all patients postoperatively,frequently potentiates severe hypertension in the anephric patient during this unstable period.
Postoperative Fluid Management and Dialysis
For anuric patients, maintenance fluid is restricted and ongoing sequestration/overt losses are replaced with crystalloids, colloids or blood products.
Treat postoperative hyperkalemia emergently until dialysis can be provided.
If early postoperative dialysis is required and the patient is hemodynamically unstable, start CVVH (continuous venovenous hemofiltration). For simple fluid overload, ultrafiltration would be sufficient.
Postoperative Analgesia for CKD patients
Management issues in postoperative pain management for CKD patients may include one or more of the following:
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Prevention of further renal damage
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Renal dose adjustment
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Issue of chronic pain:
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Primary diseases such as PCKD, gout and diabetic neuropathy
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Co-morbidity such as peripheral vascular disease
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Muscle cramps during dialysis
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Pain related to needles and catheters used in dialysis
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Painful syndromes such as calciphylaxis, nephrogenic sclerosing fibrosis, dialysis-related amyloidosis, and renal osteodystrophy
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Role of regional and neuraxial analgesia in chronic kidney disease
Analgesia for CKD Stage 1
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Neuraxial or peripheral nerve block whenever possible
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Mild pain: Acetaminophen+NSAIDs±tramadol
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Moderate to severe pain: Acetaminophen+NSAIDs+tramadol±opioids*
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Perioperative gabapentin or pregabalin as adjuvants in selected cases like trauma or neuropathic pain
Note: NSAIDs are valuable analgesic adjuncts and should not be withheld from these patients, as there is an absence of evidence to suggest that short-term therapy predisposes to any further chronic renal impairment.​
Pain management for CKD patient on dialysis
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Peripheral nerve block whenever possible
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Mild pain: Acetaminophen ± tramadol*
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Moderate to severe pain: Acetaminophen+opioids** (fentanyl or hyd romorphone)±tramadol*±ketamine
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Antiepileptics* in neuropathic pain only
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Avoid NSAIDs
Note: * - renal dose adjustment is required; ** - adjusted dose, selected opioids
Adjuvant medications are helpful for improving pain scores, reducing opioid doses and treating neuropathic components of pain in dialysis patients.
Anticonvulsant analgesics may be required for the treatment of neuropathic pain. These medications can increase the risk of sedation in dialysis patients with accumulation between dialysis sessions. Withdrawal and escalation of pain can occur after dialysis due to the wash out of these solely renal excreted medications from patients’ plasma. A small daily dose can be used on nondialysis day with an additional loading dose immediately after dialysis.
Ketamine plays an important role in managing acute and acute-on-chronic pain and can be administered through various routes, or combined with opioids in PCA pumps.
Opioids safety in End-stage renal disease
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The use of fentanyl, alfentanil and hydromorphone are relatively safe in dialysis patients but doses should be adjusted to minimize the risk of respiratory depression.
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Morphine should be avoided due to the accumulation of toxic metabolite morphine-3-glucuronide (M3G).
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Codeine, which will be converted to morphine, should also be avoided for the same reasons.
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The old concept of poorly dialyzable M3G and M6G has been changed since new studies found that hemodialysis reduces the concentration of glucoronidated metabolites of morphine after dialysis.
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Meperidine (pethidine) again needs to be avoided due to the accumulation of norpethidine, which is neurotoxic as well.
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Recommendations for the use of tramadol in dialysis dependent patients include lowering the maximum daily dose and increasing the interval between doses.
ACUTE RENAL FAILURE AND ANESTHESIA
The concept of acute renal failure (ARF) has undergone significant re-examination in recent years. Mounting evidence suggests that acute, relatively mild injury to the kidney or impairment of kidney function, manifest by changes in urine output and blood chemistries, portend serious clinical consequences. Although urine output is both a reasonably sensitive functional index for the kidney as well as a biomarker of tubular injury, the relationship between urine output and GFR and tubular injury is complex. The first description of ARF, then termed ischuria renalis, was by William Heberden in 1802.
The Acute Dialysis Quality Initiative (ADQI) group developed a system for diagnosis and classification of a broad range of acute impairment of kidney function through a broad consensus of experts. The characteristics of this system are summarized in the following figure. The acronym RIFLE stands for the increasing severity classes Risk, Injury, and Failure; and the two outcome classes, Loss and End-Stage Renal Disease (ESRD).
Acute Kidney Injury (AKI) is defined by an abrupt decrease in kidney function that includes, but is not limited to, ARF. It is a broad clinical syndrome encompassing various etiologies, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (e.g, ischemia, toxic injury); as well as extrarenal pathology (e.g., prerenal azotemia, and acute postrenal obstructive nephropathy).
AKI is common, harmful, and potentially treatable. Even a minor acute reduction in kidney function has an adverse prognosis. Early detection and treatment of AKI may improve outcomes.
AKI is defined as any of the following:
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Increase in SCr by > 0.3 mg/dl (>26.5 lmol/l) within 48 hours; or
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Increase in SCr to >1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or
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Urine volume <0.5 ml/kg/h for 6 hours.
Stage-based management of AKI
Pathophysiology of acute renal failure
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The acute decline in GFR seen in ARF is the result of combined vascular and tubular injury. Intrarenal vasoconstriction with a decrease in glomerular filtration pressure combined with vascular stasis in the outer medulla results in tubuloglomerular feedback. The reduction in blood flow seen in the outer medulla persists in the reperfusion period. Recent evidence points to the increasingly important role of arteriolar endothelial activation and leukocyte adhesion in the pathogenesis of outer medullary ischemia.
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Postischemic arterioles have increased reactivity to vasoconstrictive agents and decreased vasodilatory responses.
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Ischemia rapidly results in the loss of cytoskeletal integrity and cell polarity with shedding of the proximal tubule brush border.
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Oxygen deprivation results in intracellular ATP depletion via metabolism to ADP and AMP. ATP depletion results in profound (but initially reversible) ultrastructural changes in intracellular actin bundles resulting in loss of cytoskeletal integrity.
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During prolonged ischemia, AMP is further metabolized to hypoxanthine, which is able to diffuse freely from the cell, leading to an inability of the cell to easily resynthesize ATP during reperfusion.
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Prolonged severe oxygen depletion thus results in the inability to maintain ionic gradients and the activation of destructive enzyme systems culminating in an inflammatory necrotic process.
Differential diagnosis of acute renal failure
The salient differentiating features of prerenal, renal and post-renal causes of acute renal failure are summarised in the following table.
Risk factors for the development of perioperative renal failure
The important risk factors for the development of perioperative renal dysfunction is given in the following table.
General principles to prevent perioperative renal dysfunction
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The main priority is the prevention / further deterioration of acute renal failure, plus maintenance of an adequate urine output (1–2 ml/kg/h)— ‘non-oliguric renal failure’. Urinary catheterization should be considered early (i.e. presurgery)
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Preoperative rehydration is important in preventing ARF. Patients who are significantly dehydrated (e.g. bowel obstruction) need fluid deficit corrected prior to surgery, and this is often best judged by CVP monitoring (maintain CVP at 10–15 cmH2O)
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Optimise volume status and cardiac output
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Intravnous fluid, and/or inotropes
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Consider invasive hemodynamic monitoring and/or transesophageal echocardiography
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The response to a fluid bolus (250–500 ml) over 10–15 min may help differentiate between hypovolemia and acute tubular necrosis while more invasive monitoring is prepared.
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An adequate BP is important for renal perfusion
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A mean arterial pressure of >70 mm Hg (85 mm Hg in hypertensive patients) should be maintained (useinotropes if necessary)
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Maintain near-basal BP perioperatively
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Avoid hypovolemia
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The outcome from polyuric ARF is better than oliguric
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ARF, but no patient should be given furosemide (frusemide) until they have an adequate filling pressure and systemic arterial pressure
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Frusemide is given initially as an IV bolus of 20–40mg. In patients with established renal insufficiency (i.e. raised serum creatinine) give 250 mg over 1 hour as an infusion.
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Consider mannitol (0.5–1 g/kg IV) for vascular clamping, although there is little supporting evidence
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Monitor serum K+ 1 to 2 hourly if raised (most blood gas analysers give accurate levels).
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In patients with established ARF, further acid-base deterioration should be avoided. Plan for perioperative renal replacement therapy.
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Any abdominal surgery or infection contraindicates peritoneal dialysis and a dialysis catheter should be inserted whilst the patient is still anesthetized.
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Avoid nephrotoxic antimicrobials, or optimize schedule and formulation
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Avoid NSAIDs in patients at risk
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Avoid contrast studies, or give N-acetylcysteine, bicarbonate (Sodium bicarbonate in rhabdomyolysis prevents myoglobin precipitation in the renal tubules by maintaining an alkaline urine); consider ultrafiltration when indicated.
Role of creatinine as a marker of perioperative renal dysfunction
Serum creatinine concentration, the most commonly used marker of renal function is insensitive to acute changes in GFR. An acute reduction in GFR as great as 50–70% can occur without an immediate increase in serum creatinine concentration. Other changes during the postoperative period (e.g. intravascular haemodilution, variable muscle mass and changes in metabolic rate), complicate the interpretation of serum creatinine measurements.
Measurement of GFR in the postoperative period using conventional creatinine clearance tends to overestimate GFR due to tubular secretion of creatinine.
Biomarkers after acute kidney injury (AKI)
Schematic representation of the levels of several biomarkers over time. The baseline (time 0) is immediately after cardiac bypass (CBP).
The lines are a schematic of the predicted rise and fall of the biomarkers after CBP as a function of time and when levels become significant enough to cross the threshold for diagnosing AKI. These patterns and specifically the timeline for diagnosing AKI represent ideal circumstances (the shortest possible time interval shown in a clinical study) and not necessarily what will prove to be clinically verifiable.
Cystatin-C = serum cystatin C;
IGFBP7 = insulin-like growth factor binding protein 7;
KIM-1 = kidney injury molecule-1;
nGaL = neutrophil gelatinase-associated lipocalin;
TIMP-2 = tissue inhibitor of metalloproteinase 2.
Postoperative Care
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Avoid NSAIDs in all patients at risk of renal failure.
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Give appropriate IV fluids and avoid dehydration (consider CVP monitoring if not instituted).
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Closely monitor urine output.
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If oliguria occurs (< 0.5 mL/kg/h) try a fluid challenge of 250–500 mL 0.9% saline/colloids, or mannitol (0.5–1 g/kg IV).
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Consider CVP and adequate arterial pressure as previously.