Anaesthesia in chronic dialysis patients: A narrative review

Abstract

The provision of anaesthesia for individuals receiving chronic dialysis can be challenging. Sedation and anaesthesia are frequently managed by critical care clinicians in the intensive care unit or operating room. This narrative review summarizes the important principles of sedation and anaesthesia for individuals on long-term dialysis, with reference to the best available evidence. Topics covered include the pharmacology of anaesthetic agents, the impacts of patient characteristics upon the pre-anaesthetic assessment and critical illness, and the fundamentals of dialysis access procedures.

Key Words: Dialysis; Sedation; Critical care; Anaesthesia; Intensive care; Pharmacology; Renal impairment

Core Tip: Patients on chronic dialysis have increased perioperative and anaesthetic risks. Sedative and analgesic agents must be titrated appropriately. The optimal blood pressure targets are unknown but may be higher than for the general population. Caution is necessary with electrolyte and fluid management. A detailed pre-anaesthesia evaluation is particularly important in this patient group.

INTRODUCTION

Patients receiving long-term dialysis are affected by higher rates of morbidity, critical illness, healthcare utilization, unplanned surgery, intensive care unit (ICU) admission, adverse ICU and perioperative outcomes, and mortality[1,2]. The medical complexity of this patient group means that the delivery of sedation or anaesthesia in the ICU or operating room can be challenging. Although critical care clinicians may frequently be required to provide care to chronic dialysis patients, data to guide the best approach to anaesthetic techniques are lacking.

This narrative review discusses the important principles of sedation and anaesthesia in chronic dialysis patients. It is intended as a practical primer for physicians practicing in both elective perioperative and acute high-dependency settings. Evidence-based recommendations are incorporated where available. The term ‘critical care physician’ is used throughout this article to collectively describe anaesthetists, intensivists, and other physicians involved in a critical care setting. Individuals receiving maintenance intermittent haemodialysis (HD) for end-stage renal failure are referred to as ‘chronic dialysis patients’.

A structured search of the PubMed database was undertaken from inception to August 2024 using a range of applicable search terms in various combinations, such as “critical care”, “dialysis patient”, and “anaesthesia”. Results were screened for relevance. A broad selection of articles was obtained, including clinical trials, commentaries, and case series. Additional papers were retrieved by manually searching guidelines or article reference lists. Articles were limited to the English language. Results of the literature search were synthesized to generate this narrative review.

PHARMACOLOGY IN RENAL IMPAIRMENT

The kidney is responsible for the metabolism and excretion of many drugs. Other crucial routes of drug metabolism and elimination include hepatic and pulmonary clearance. The mechanisms of drug elimination by the normal kidney include glomerular filtration, tubular secretion and passive diffusion. The pharmacologic agents used for sedation and anaesthesia, such as certain sedatives and anxiolytics, may be affected by reduced renal clearance and dialysis. Renal impairment can influence both pharmacokinetics and pharmacodynamics. For example, uremia can increase drug target site sensitivity; in such cases, pronounced drug effects are seen at lower doses. The volume of distribution is frequently altered due to reduced protein binding and increased body water.

Failure to properly adjust for renal insufficiency increases the risk of dose-related adverse effects. Adjustment can involve reduced dosages or frequencies. Due to the complexity of renal drug dosing, especially in the context of renal replacement therapy, a drug reference manual should be checked when uncertain. However, dose recommendations are typically based on low-quality data, and prescriptions must be individualized and titrated appropriately.

Most of the pharmacologic agents used for the induction and maintenance of anaesthesia are not efficiently cleared by dialysis. In this situation, drug administration is not influenced by the timing of dialysis per se. For agents that are dialysable, however, higher dosing or timed dosing following treatment may be needed. Many factors influence drug dialysability, such as the type of renal replacement therapy, protein binding, and volume of distribution[3]. Sedatives, for instance, are generally highly protein-bound and not amenable to removal through dialysis.

The relevance of renal impairment to sedative and analgesic agents that are common in critical care is summarized in Table 1[4-25]. Many institutions have dosing protocols for opioid analgesics in renal impairment, but guidelines for use of anaesthetic agents are uncommon. In general, there is limited kidney metabolism and initial boluses can be prescribed as usual while prolonged infusions should be monitored and titrated cautiously. Although this review focusses on individuals reliant on HD, most pharmacologic precautions apply similarly to individuals undergoing peritoneal dialysis (PD); however, patients on PD typically have higher preserved intrinsic renal function than chronic HD patients and drug clearance is significantly less efficient through PD than HD.

Table 1 Pharmacologic considerations for common anaesthesia agents in chronic dialysis patients.

Drug	Dose change in renal Impairment	Dialysable	Comments
Sedatives
Propofol	-	No	Metabolized by the liver. No dose adjustment is necessary for any degree of renal impairment[4-7]. Because metabolites theoretically accumulate with longer infusions, vigilance is advised
Ketamine	-	No	Metabolized by the liver. No dose adjustment is necessary for any degree of renal impairment
Thiopentone	↓	No	Predominantly undergoes hepatic metabolism with urinary excretion of metabolites. Dose must be reduced by 25%-30%[8]. Clearance via haemodialysis is negligible[9]
Etomidate	-	Unknown	Rapid metabolism in the liver and plasma. No dose adjustment is necessary
Midazolam	↓	No	Predominantly undergoes hepatic metabolism with urinary excretion of metabolites. Boluses can be administered without any dose adjustment[10]. Continuous infusions require lowered doses. Metabolites accumulate with extended use, resulting in a prolonged half-life and sedative effect[11-13]. However, the effect is inconsistent with significant interpersonal variability
Volatile Gases	-	Unknown	Primarily eliminated via exhalation (e.g. halothane, desflurane, sevoflurane); renal excretion is minor. No dose adjustment is necessary for any degree of renal impairment[6,14,15]
Analgesics
Morphine	↓	Yes	Metabolized through hepatic glucuronidation with urinary elimination of metabolites. Morphine metabolites accumulate with renal dysfunction, resulting in a prolonged half-life. A 75% reduction is recommended for both bolus and infusion doses[16-18]. No opioids are dialysable in subjects with preserved kidney function because intrinsic clearance exceeds the rate of removal via dialysis. Morphine is considered dialysable in those with advanced kidney impairment; however, extracorporeal removal is rarely indicated in practice due to the success of supportive care and naloxone as an antidote[3]
Oxycodone	↓	Yes	Undergoes hepatic glucuronidation. Metabolites accumulate with renal impairment. Dose should be reduced by 25%-50%
Fentanyl	-	No	Hepatic metabolism followed by mainly urinary clearance. Because of its short half-life, accumulation occurs only with continuous use. No dose adjustments are required for bolus dosing[19]. Continuous infusion doses should be reduced by approximately 25-50%[17,20]
Remifentanil	-	No	Rapidly metabolized by blood and tissue enzymes, with metabolites excreted in the urine. No dose adjustment is necessary
Paralytics
Suxamethonium	-	Unknown	Suxamethonium is hydrolyzed rapidly and undergoes minimal urinary excretion. No dose adjustments are required. Be aware of the risk of hyperkalaemia
Rocuronium	-	Unknown	Undergoes hepatic metabolism followed by biliary and renal excretion. No dose adjustments are typically recommended in patients with renal impairment; however, this interaction is poorly understood. In some experimental studies of patients with renal failure, clearance was reduced by a third and half-life was extended by up to 50%. Therefore, rocuronium is best avoided where prolonged paralysis is undesirable[21-23]. Sugammadex reversal is contraindicated due to insufficient safety data in chronic dialysis patients
Cisatracurium	-	Unknown	No dose adjustment is necessary. Although the half-life is nominally increased in kidney failure, cisatracurium is rapidly metabolized via Hofmann degradation
Regional Anaesthetics
Lidocaine	-	No	No dose adjustments for kidney function are required when used for local or regional anaesthesia. Spinal and epidural regional anaesthesia, such as with ropivicaine or bupivacaine, appears safe in chronic dialysis patients[24,25]

PRE-ANAESTHETIC ASSESSMENT

A thorough assessment before the administration of sedation or general anaesthesia in the chronic dialysis patient is imperative to reduce risks and optimize patient tolerability and outcomes. Chronic dialysis patients have a higher incidence of comorbidities and anaesthetic complications than the general population. There are increased rates of cardiovascular disease, coagulopathy, frailty and polypharmacy. The likelihood of ICU mortality is 50% higher than for individuals without renal impairment[1,2]. There are higher rates of perioperative complications such as hypotension, pulmonary oedema, arrhythmia, neurologic injury, and bleeding[26,27]. Chronic dialysis patients are also significantly more likely to require perioperative vasopressors and mechanical ventilation[28].

ANAESTHETIC RISK TOOLS

The application of anaesthetic, disease severity or surgical risk tools will vary with clinical contexts. Chronic dialysis patients have worse illness severity on admission to the ICU, and assessment tools such as Acute Physiologic and Chronic Health Evaluation and Sequential Organ Failure Assessment can be utilized with reasonable accuracy[29]. Reduced functional and exercise tolerance, which is associated with increased anaesthetic and postoperative mortality[30], can be evaluated with standard methods such as the Duke Activity Status Index questionnaire or determination of a patient’s metabolic equivalent of tasks. The American Society of Anaesthesiologists (ASA) physical status classification, which predicts perioperative complications across a range of settings, immediately categorizes chronic dialysis patients as high-risk. Renal dysfunction is also frequently incorporated into surgical risk equations, such as the American College of Surgeons Surgical Risk Calculator[31], Revised Cardiac Risk Index[32], Gupta Myocardial Infarction or Cardiac Arrest[33], National Emergency Laparotomy Audit[34], and EuroSCORE[35] tools.

PREOPERATIVE TESTS

Selective preoperative testing should be undertaken, based on medical status, the planned intervention and the likelihood that the test will improve treatment and outcomes. The thoroughness of testing will be dictated by clinical urgency; for instance, there will be a greater opportunity to perform preparatory testing before elective anaesthesia cases than before a rapid sequence induction in the emergency department. Although pre-anaesthesia tests are requested routinely, there are limited data to confirm the utility of this practice[36,37].

The National Institute for Health and Care Excellence guidelines outline the minimum required tests prior to anaesthesia[38]. For patients graded as ASA 3, which is elevated risk and includes all chronic dialysis patients, a serum biochemistry and electrocardiogram are recommended before minor surgeries. For major surgery, a full blood count and coagulation studies are also recommended. An echocardiogram is recommended in most individuals regardless of the type of surgery. As the need for sedation and ventilation for acutely unwell medical patients in the ICU is less predictable than operating theatre conditions, limited pre-anaesthesia testing is performed on a case-by-case basis.

AIRWAY ASSESSMENT

A detailed pre-anaesthesia airway assessment should be conducted. Individual examination findings and tests lack sensitivity and specificity for a difficult airway[39], but a combination is typically useful[40]. Chronic dialysis patients are more likely to have an anatomically difficult airway, with a higher incidence of dental disease[41] and higher Mallampati scores[42]. The incidence of obesity appears to be equivalent to the general population[43]. Chronic dialysis patients are also predisposed to a physiologically difficult airway because of the sequelae of kidney disease and other comorbidities. For example, obstructive sleep apnoea and gastroparesis are significantly more common than in the matched population[44-46]. In small retrospective studies, failed extubation and difficult ventilatory weaning were found to be 2-5 times more frequent in patients receiving HD, usually due to pulmonary congestion[47,48].

VASCULAR ACCESS

Obtaining reliable intravenous access can be difficult in individuals with a history of multiple HD catheters or fistula interventions. It is expert opinion that peripheral intravenous canulae should be sited away from an arteriovenous fistula (AVF), ideally on the contralateral limb. However, there is no evidence that cannulation of or near an AVF in emergency situations is detrimental. Where central venous access is planned, femoral catheters may be preferred for short-term indications to avoid traumatizing neck vessels. The subsequent development of central vein thrombosis or stenosis jeopardizes the viability of upper limb AVF. Peripherally inserted central catheters are also discouraged to preserve upper limb veins. Radial intra-arterial lines are generally disadvised to prevent arterial occlusion or aneurysm formation and to protect AVF patency, though supporting evidence is absent.

HAEMODYNAMIC AND VENTILATORY MANAGEMENT

Cardiovascular and respiratory support during the provision of sedation and anaesthesia in the ICU or operating room can be complicated in the dialysis population. In particular, there are implications for fluid management, haemodynamic targets and acid-base balance, and ventilator settings.

RESPIRATORY SUPPORT

Abnormal cardiopulmonary physiology is frequently demonstrated, requiring an attentive and individualized approach. Acute or chronic pulmonary oedema is prevalent and necessitates higher positive end-expiratory pressure during mechanical or non-invasive ventilation, usually of at least 5-10 cmH₂O. Individuals who are dialysis-dependent appear to show higher plateau pressures and poorer lung compliance[49]. Settings for tidal volume and airway pressure may be affected by a restrictive ventilatory defect, which is often multifactorial and related to congestion, myopathy and metabolic bone disease[50].

CARDIOVASCULAR SUPPORT

The best approach to blood pressure management in chronic dialysis patients is uncertain. Most patients are conditioned to hypertension at baseline and there is no high-level evidence to support an optimal long-term blood pressure goal. The optimal blood pressure targets for chronic dialysis patients with critical illness or undergoing surgery are unknown. Although it is widely thought that abrupt normotension in subjects who are hypertensive at baseline may induce a state of relative hypoperfusion, the benefit of raised mean arterial pressure (MAP) targets has not been confirmed. Until data arise to substantiate otherwise, the aim in shocked or vasoplegic adult chronic dialysis patients should usually be a MAP of 60-70 mmHg, consistent with practices in the general population.

Vasopressors and inotropic agents are frequently required. There is no evidence that the uraemic state itself alters vasopressor responsiveness or the relative efficacy of one drug vs another. The choice of inotrope or vasopressor in chronic dialysis patients should therefore be guided by indication and clinical circumstances. For example, noradrenaline should remain the first-line agent in sepsis and dobutamine should remain a preferred agent in cardiogenic shock. Because of the comorbidity profile of the chronic dialysis patient population, the threshold for invasive haemodynamic monitoring, whether intraoperatively or in the ICU, may be lower. The treatment of shock in this group merits further research.

The acute management of hypertension is similar to that for the general population. The rate and degree of blood pressure reduction, and the pharmacologic therapies employed, depend on the medical indication. Standard options for acute blood pressure lowering, such as intravenous beta blockers, are commonly used. Because volume overload is the primary driver of hypertension in the dialysis patient cohort, particular benefit may be achieved with intravenous vasodilators like nitroglycerin or, in those with residual urine output, with diuretics.

FLUID REPLACEMENT

Chronic dialysis patients are constantly vulnerable to hypervolaemia. The volume of intravenous fluid given in the ICU or intraoperatively, including for rehydration or medication administration, should be recorded. Fluid boluses must be used judiciously in resuscitation scenarios and maintenance intravenous therapy should be minimized. Because chronic dialysis patients are typically restricted to a daily fluid intake of around 1 L, additional ultrafiltration will invariably be required perioperatively or for those in the ICU.

No prospective trials have confirmed the superiority of one fluid type over another in the resuscitation of chronic dialysis patients with shock. Crystalloid solutions are prescribed more frequently than colloids. Compared with balanced crystalloid solution, 0.9% sodium chloride slightly increases the incidence of hyperchloraemic acidosis but not hyperkalaemia[51,52].

DIALYSIS SCHEDULING

Chronic dialysis patients must continue to receive renal replacement therapy throughout the course of their critical illness. Routine HD treatments must be organized around other ICU interventions or the operating theatre schedule. Frequent biochemical monitoring is needed. Additional HD sessions may be necessary pre-emptively or reactively to optimize physiology, including correction of volume overload or electrolyte and acid-base disturbances. HD should be provided soon before and after major interventions, as longer intervals between dialysis and surgery are associated with increased postoperative complications and mortality[53].

PD is usually continued as normal where practicable, but extra exchanges may periodically be necessary to achieve greater clearances or ultrafiltration. The abdomen should be drained to empty prior to endotracheal intubation or any surgeries. PD patients usually have a residual urine output, so diuretics can be trialled where hypervolaemia is problematic. Bridging HD should be planned in some cases, such as severe metabolic disturbances or after abdominal surgery.

Intraoperative HD may rarely be necessary, but is technically and logistically challenging and should be avoided where possible. Retrospective studies have not shown intraoperative HD to be beneficial; however, patients in this situation are critically unwell and may benefit on a case-by-case basis. The commonest use for intraoperative HD is liver transplantation and the commonest modality is continuous renal replacement therapy.

PERIOPERATIVE MEDICINE

Medical specialists and critical care clinicians are commonly responsible for perioperative medical optimization. The principles of perioperative medicine are similar for chronic dialysis patients as for the general population (Table 2). These principles can also be adapted to relevant procedures undertaken in the ICU. Elements of routine daily supportive care in the ICU, such as deep vein thrombosis prophylaxis and ulcer prophylaxis, can also be applied across most patient populations[54-56].

Table 2 Perioperative medical management of the chronic dialysis patient.

Medical issue	Practice points
Glycaemic control	The perioperative blood glucose goal is usually between about 5-10mmol/L[55]. Guidelines recommend a glycaemic target of 7.8-10 mmol/L for critically ill adults[56]. Pre-existing insulin and oral anti-hyperglycaemic drugs are frequently withheld or reduced
Antihypertensives	Blood pressure targets are uncertain. Usually continued perioperatively and during acute illness unless hypotension is problematic
Antithrombotics	There should be an antithrombotic medication management plan where feasible. The intention is to balance the risk of surgical bleeding if the antithrombotic is continued with the risk of thromboembolism if withheld. Due to the complexity of decision-making, guidelines and local policies should be followed
Bleeding reversal and transfusions	Spontaneous and postoperative bleeding rates are significantly increased. Bleeding diathesis is predominantly explained by uraemic platelet dysfunction and the frequent use of anti-thrombotic medications. Haemodialysis reduces the bleeding time and prevents haemorrhagic complications[54]. Options to reverse acute haemorrhage include intravenous calcium, desmopressin, and tranexamic acid, and acute haemodialysis; however, clinical studies are scant. Consider empiric protamine where heparins are used for anticoagulation in dialysis. Transfusion protocols guided by bedside viscoelastic assays are advocated but have not been studied in this context. Erythropoietin-stimulating agents have no role in acute anaemia management. Where a blood transfusion is necessary in a potential candidate for kidney transplantation, leukocyte-depleted allogenic red blood cells are preferred
Neuraxial anaesthetic blocks	Renal impairment is associated with a slightly increased risk of epidural haematoma with neuraxial procedures[58], but objective data are scarce. The approach to regional anaesthesia relies on clinician judgement and standard anaesthesia and preoperative guidelines[38]. Experts recommend ensuring a low plasma urea and heparin-free dialysis near the time of the procedure

RENAL VASCULAR ACCESS OPERATIONS

Critical care clinicians should possess a working knowledge of the archetypal renal dialysis access procedures. The procedures are outlined in Table 3. Dialysis access procedures may be performed in dedicated suites or at the bedside, in either an acute or elective setting. Depending on local practices, critical care clinicians may be involved with performing the procedure, rendering the anaesthetic, or managing the post-surgical care.

Table 3 Common dialysis access procedures.

Surgical procedure	Technical notes	Anaesthetic techniques
Arteriovenous fistula creation	Surgical construction of a connection between an artery and vein to enable repeated cannulation for chronic haemodialysis. Typically in the upper limb. Elective procedure	Local anaesthesia. Regional anaesthesia (e.g. brachial plexus block). Sedation or general anaesthesia
Tunnelled haemodialysis catheter insertion	Insertion of a central venous catheter, usually in the internal jugular vein, which is tunnelled through a subcutaneous tract. Similar to a standard uncuffed central venous line placement. Urgent or elective procedure	Local anaesthesia. Sedation
Peritoneal dialysis catheter insertion	Implantation of a catheter into the peritoneal cavity, which is then tunnelled through a subcutaneous tract. Both surgical and percutaneous radiologic methods are used. Elective procedure	Local anaesthesia. Sedation or general anaesthesia

An understanding of the perioperative aspects of acute kidney transplantation is also important. In the United States, approximately 10% of patients are admitted to the ICU following kidney transplant surgery[57]. Chronic dialysis patients account for the significant majority of kidney transplant recipients. Kidney transplantation is an open extra-peritoneal surgery performed under general anaesthesia. The operation time is typically around 3 hours and there is usually minimal blood loss. Attention to volume status is essential; intravenous fluid must be delivered in quantities sufficient to perfuse the new graft and avoid hypotension without causing volume overload. The urine output is a reliable guide. A central venous catheter is usually placed to facilitate intravenous fluids, the frequent and complex perioperative dosing of immunosuppressive therapies, and regular blood draws for electrolyte and creatinine monitoring. Regional transplant center protocols are typically available. Postoperative pain can be significant and intravenous analgesia may be requested[58].

CONCLUSION

Patients on chronic dialysis have increased perioperative and anaesthetic risks. Careful titration of sedative and analgesic agents is required. Chronic dialysis patients frequently demonstrate abnormal cardiorespiratory physiology, which affects ventilator and fluid management. A thorough pre-anaesthesia evaluation is essential to minimise risks and improve patient outcomes.