Renal/hepatic disorders during pregnancy

What the Anesthesiologist Should Know before the Operative Procedure

Pregnancy creates moderate physiologic changes in both the renal and hepatic systems. These changes can make the diagnosis of new renal or hepatic impairment difficult at times. With 7.4 million people in the United States being affected by kidney disease and 400,000 diagnosed with chronic liver disease, it is not uncommon to see a parturient with one of these preexisting disease states. A disruption in the renal or hepatic system can wreak additional physiologic havoc on a pregnant woman’s body. Parturients with cirrhosis are at a higher risk for cesarean delivery, gestational hypertension, placental abruption, and uterovaginal hemorrhage. Therefore, an anesthesiologist must possess thorough knowledge of common renal and hepatic disorders before administering anesthesia to a parturient.

1. What is the urgency of the surgery?

What is the risk of delay in order to obtain additional preoperative information?

If the mother or fetus is at risk, emergency surgery should not be delayed. However, the potential risk of the operation should be communicated to the mother. For instance, a cirrhotic patient with a MELD (Model of End stage Liver Disease) >14 who undergoes emergent abdominal surgery possesses a three month mortality between 50%-80%. If the surgery is urgent or elective, time should be taken to optimize the pregnant patient. This optimization includes the improvement of electrolyte, volume, and coagulation status. If a pregnant patient with renal or hepatic disease arrives for a cholecystectomy or appendectomy with extreme volume overload, electrolyte disturbances, and coagulopathy, this patient should likely receive emergent hemodialysis and be transfused with fresh frozen plasma and platelets as indicated by clotting studies.

If a parturient has received a renal or hepatic transplant, preoperative assessment of the transplanted organ should be obtained. If the organ is functioning normally, intraoperative goals include maintenance of perfusion pressure to the transplanted organ as well as appropriate antibiotic prophylaxis. These patients will likely be immunosuppressed and meticulous attention to avoidance of infection is paramount to the parturient’s perioperative management.

Emergent: If mother or fetus are in grave distress, emergency surgery may be warranted. Issues related to emergency surgery depend on the severity of the preexisting renal or hepatic conditions. In the setting of renal dysfunction, both volume overload and electrolyte disturbances may be encountered. In the setting of hepatic impairment, volume overload, electrolyte disturbances, and coagulopathy can be anticipated.

Urgent: If time exists prior to an urgent surgery, optimization of the volume and coagulation status should be undertaken. This may include emergent hemodialysis as well as the administration of clotting products.

Elective: Elective surgery in a parturient with significant renal or hepatic dysfunction should likely be avoided until after pregnancy.

2. Preoperative evaluation

Patients with renal or hepatic disease often possess multiorgan dysfunction. A thorough workup looking for coexisting lung disease (hepatopulmonary or portopulmonary syndrome), cardiac disease (heart failure, cirrhotic cardiomyopathy), central nervous system disease (encephalopathy, uremia), and gastrointestinal disease (portal hypertension) should be undertaken. This workup should include a full metabolic panel, a complete blood count, full coagulation studies (to include a thromboelastogram if possible), an electrocardiogram, a chest x-ray, and an upper endoscopy. An echocardiogram should be considered if the liver disease is extremely advanced or if the operative case will induce significant cardiac stress.

Medically unstable conditions warranting further evaluation include cardiac instability resulting from volume overload, pulmonary hypertension, and hyperkalemia.

Delaying surgery may be indicated if the above cardiac states are present or profound bleeding secondary to endogenous coagulopathy.

3. What are the implications of co-existing disease on perioperative care?

As mentioned previously, chronic renal and hepatic disease can lead to multiorgan dysfunction. This multiorgan involvement necessitates a thorough preoperative workup to better assess the status of each organ system.

b. Cardiovascular system

Patients with cirrhosis may have a hyperdynamic state consisting of increased cardiac output and decreased systemic vascular resistance. The decreased SVR is postulated to result from numerous systemic arteriovenous shunts as well as an increase in endogenous vasodilators. Cardiac output increases to compensate for this decreased SVR. Patients normally exhibit low-normal blood pressures. As well, parturients may have decreased plasma oncotic pressure due to decreased synthesis by the liver and decreased effective arterial blood volume.

Anesthetic management goals include restoration of the effective arterial blood volume and the addition of vasoconstrictive medications to offset the decreased systemic vascular resistance. The response to vasoconstrictors is blunted with cirrhosis.

If severe renal disease is present, diuresis and inotropic support may be necessary to combat potential heart failure from volume overload. Renal disease/uremia can also result in conduction abnormalities.

c. Pulmonary

Parturients may have baseline hypoxemia from hepatopulmonary syndrome (HPS). HPS, with clinical features of platypnea (shortness of breath or dyspnea that is relieved when lying down, and worsens when sitting or standing up) and orthodeoxia (fall in arterial blood oxygen on assuming the upright posture that is usually caused by right-to-left cardiac or vascular shunting with a posturally induced fall in left-sided pressure permitting a corresponding gradient across the shunt), results from further intrapulmonary arteriovenous shunting of blood. There may also be hypoxemia secondary to a further decrease in their functional residual capacity from excessive intra-abdominal volume from ascites. This is exacerbated by pregnancy and the gravid uterus.

Anesthetic management issues include addition of positive end expiratory pressure as well as reverse Trendelenberg positioning in order to reexpand collapsed alveoli.

Portopulmonary hypertension may also be present resulting in elevated pulmonary artery pressures (mean PAP >25 mm Hg).

Unless volume overload is present, renal disease does not significantly affect pulmonary function.

d. Renal-GI:

Patients with cirrhosis often have portal hypertension. This places them at risk for gastrointestinal bleeding. The addition of portal vasoconstrictive agents, such as vasopressin, beta blockers, and somatostatin may be beneficial.

Renal dysfunction is also quite common with advanced liver disease, almost always resulting from renal hypoperfusion. Preservation of renal blood flow in a parturient with cirrhosis is critical to prevent further decreases in renal function. If severe renal dysfunction is already present, hemodialysis may be necessary.

Parturients with preexisting renal disease may have a further worsening of their delayed gastric emptying. Full stomach precautions should always be practiced. Nephrotoxic agents (NSAIDs, aminoglycosides, anticholinergics, and radiocontrast dyes) should be avoided.

A preoperative endoscopy should be performed to assess for varices.

e. Neurologic:

Both liver and renal disease can result in significant encephalopathy. Acute fulminant liver failure can result in a precipitous rise in intracranial pressure secondary to cytotoxic edema. If severe confusion is present from encephalopathy, prophylactic or prolonged intubation may be necessary for airway protection.

f. Endocrine:

Parturients with liver disease are susceptible to hypoglycemia and hyponatremia. Perioperative glucose monitoring is essential when caring for a cirrhotic patient as their blood sugars can be quite labile. Parturients with renal disease may present with hyperglycemia (from preexisting diabetes) as well as secondary hyperparathyroidism (increased calcium, decreased phosphorous).

g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (eg. musculoskeletal in orthopedic procedures, hematologic in a cancer patient)

Both advanced renal and hepatic disease can result in significant hematologic impairment. Parturients with cirrhosis may present with anemia, thrombocytopenia, and neutropenia. They are often coagulopathic from decreased factor synthesis. Parturients with chronic renal disease may also have anemia from decreased erythropoietin production. Renal disease can induce a coagulopathic state secondary to decreased qualitative platelet function (resulting from decreased expression of von Willebrand’s factor).

Baseline clotting studies should be obtained and blood products should be available for labor as well as cesarean section.

If a parturient tests positive for hepatitis B, the fetus must be vaccinated.

4. What are the patient's medications and how should they be managed in the perioperative period?

Patients with advanced liver disease will be on a fairly standard medication regimen. This includes diuretics to control fluid overload (furosemide and spironolactone), antiencephalopathics to reduce confusion (rifaximin and lactulose), acid reducers (proton pump inhibitors) to control acid reflux, and beta blockers to reduce shear stress on esophageal varices. None of these medications are well studied in pregnancy. During pregnancy, these medications should be titrated to the parturient’s symptoms.

Patients with advanced renal disease are typically on erythopoetin to augment red blood cell production, calcium and phosphorous binding agents to combat hypercalcemia and hyperphosphatemia, and antihypertensives. Again, these medications should be titrated to the parturient’s laboratory values as well as symptoms. In the case of hypertension, ACE inhibitors should be avoided during pregnancy as they are known teratogens.

If a hepatic or renal transplant patient becomes pregnant, continuation of the antirejection medications is necessary. Again, these medications are not well studied in the setting of pregnancy. Mothers should be warned that pregnancy in the setting of a previous liver or kidney transplant carries increased risks. In two studies, from the Universities of Colorado and Pittsburgh, mothers with previous liver transplants fared well. Only 2 of 30 patients developed chronic rejection. Mothers with a previous renal transplant also fared well with only 15% experiencing persistent renal impairment. Other risks after transplant include a higher incidence of preeclampsia and cesarean delivery, fetal growth restriction (IUGR), and preterm delivery. Delivery of transplanted mothers should only be carried out in a high-risk center that possesses a multidisciplinary team.

h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern?

If the renal or hepatic dysfunction necessitates teratogenic medications, the mother should be informed of the risk-benefit ratio. The most commonly employed established teratogen in this scenario are ACE inhibitors. Parturients should be changed to an alternative antihypertensive medication. Long-term beta blocker use has been associated with intrauterine growth restriction, although there is less concern with the beta-1 specific agents versus propranolol. Alternative esophageal varices management (banding, sclerotherapy) may be preferred over propranolol during pregnancy.

If the parturient develops preeclampsia (likely resulting from their renal disease), vasoconstrictive agents such as the methylergonovines should be used with care as they can precipitate a hypertensive crisis.

Anticoagulation should be used cautiously as both populations have a tendency toward bleeding disorders.

i. What should be recommended with regard to continuation of medications taken chronically?

Cardiac: All cardiac medications should be continued with the exception of ACE inhibitors and beta blockers.

Pulmonary: All pulmonary medications should be continued.

Renal: All renal medications should be continued.

Neurologic: Anticonvulsants such as phenytoin and valproic acid are associated with fetal hydantoin syndrome and neural tube defects.

Alternative seizure prophylaxis should be considered. Antiencephalopathics are not well studied in pregnancy, but should be titrated to a patient’s symptoms.

Antiplatelet: Should be avoided in patients with renal and hepatic disease as both are at risk for platelet dysfunction with resultant hemorrhage.

Psychiatric: Continue medications with the exception of lithium.

Antibiotics: Some liver failure patients are on chronic antibiotic therapy for spontaneous bacterial peritonitis prophylaxis. Fluoroquinolones and aminoglycosides should be avoided in this setting as they are teratogenic.

Immunosuppressants: All immunosuppressants must be continued in the peripartum period.

j. How To modify care for patients with known allergies –

No known unique allergies.

k. Latex allergy- If the patient has a sensitivity to latex (eg. rash from gloves, underwear, etc.) versus anaphylactic reaction, prepare the operating room with latex-free products.

Latex allergies can potentially be a problem in any patient who has undergone numerous surgical procedures. Parturients with transplants should always be questioned regarding potential latex allergy.

l. Does the patient have any antibiotic allergies- – Common antibiotic allergies and alternative antibiotics]

Antibiotic allergies should be handled in the normal fashion.

m. Does the patient have a history of allergy to anesthesia?

Malignant hyperthermia (MH)

Documented: avoid all trigger agents such as succinylcholine and inhalational agents.

• Proposed general anesthetic plan:

• Ensure MH cart available:

• Family history or risk factors for MH

5. What laboratory tests should be obtained and has everything been reviewed?

Parturients with cirrhosis or chronic renal insufficiency (CRI) may possess a variety of laboratory abnormalities. Therefore, a comprehensive range of laboratory studies should be obtained.

Hemoglobin levels: Patients are often anemic with a hemoglobin level less than 8 mg/dL. A platelet count should also be obtained as advanced liver disease results in profound thrombocytopenia.

Electrolytes: Electrolytes should be evaluated to assess renal function (BUN/creatinine), bicarbonate (potential acidemia), sodium, and potassium levels.

Coagulation panel: A coagulation panel consisting of a prothrombin time, partial thromboplastin time, and thromboelastogram should be obtained. Cirrhotic patients may have or develop significant abnormalities in their coagulation parameters

Imaging: Prior to a high-risk surgery, cardiac stress testing is warranted (using pharmacologic methods or exercise). A baseline chest x-ray is important to rule out hydro or hemo thorax.

Other tests:Bilirubin, liver function tests, and albumin should also be ordered to have baseline values and to assess the liver’s synthetic functions.

Intraoperative Management: What are the options for anesthetic management and how to determine the best technique?

If a parturient requires obstetric or nonobstetric surgery, both general and regional anesthesia should be considered. Certain cases lend themselves to a preferred technique (e.g., general anesthesia for in utero fetal surgery, maternal laparoscopic surgery, or maternal thyroid surgery). However, many surgeries are amenable to either type of anesthesia. The goal is always to provide the safest option for both mother and fetus. Recent data have shown that general anesthesia carries only a slightly higher mortality (5:1,000,000 compared to 3:1,000,000) compared to regional anesthesia for cesarean section. The comorbid states of these parturients secondary to their hepatic and renal disease must be considered when deciding upon an anesthetic option.

a. Regional anesthesia

Regional anesthesia is an excellent option for any mothers undergoing a peripheral or open abdominal procedure. Suitability for regional anesthesia must be assessed in the setting of advanced liver or kidney disease, especially with regard to coagulation status.

Neuraxial

Benefits: The benefits of neuraxial anesthesia are many. The avoidance of general anesthesia improves postoperative nausea and vomiting issues. Neuraxial anesthesia techniques potentially avoid any pregnancy induced airway-related issues. If mental status changes or encephalopathy are present from cirrhosis, regional anesthesia also helps avoid any worsening of postoperative cognitive dysfunction seen with general anesthesia. Neuraxial anesthesia can also provide a more targeted and superior mode of postoperative analgesia. Pain medications are typically metabolized in the liver and/or excreted in the kidney. Avoidance of systemic pain medications by using neuraxial anesthesia can be quite beneficial.

Drawbacks: The biggest drawback or contraindication to neuraxial anesthesia is the potential coagulopathy associated with liver and kidney disease. Coagulation status must be assessed before performing neuraxial anesthesia. ASRA guidelines should be employed.

Peripheral nerve block

Benefits: The benefits of a peripheral nerve block are similar to those of neuraxial anesthesia: the avoidance of general anesthesia, the improvement in postoperative nausea and vomiting, the avoidance of airway-related issues, and superior, well-targeted analgesia.

Drawbacks: Many surgical procedures, including cesarean delivery, are not amenable to peripheral nerve blocks. The drawbacks of peripheral nerve block include a very small chance of temporary paresthesias (3%-4%) and a smaller chance of permanent nerve damage (1:10,000). Deeper plexus blocks, such as lumbar plexus or paravertebral blocks should follow the same anticoagulation guidelines as neuraxial blocks. If a patient has chronic renal insufficiency secondary to diabetes, peripheral neuropathy should be assessed. It is well established that performing peripheral nerve blocks on patients with preexisting neuropathies can be dangerous.

b. General anesthesia

General anesthesia can be very effective for parturients with liver or kidney disease.

Benefits: The benefits of general anesthesia include total amnesia and potentially more ideal surgical conditions.

Drawbacks: In the setting of hepatic or renal disease, general anesthesia can result in worsening of postoperative encephalopathy. If general anesthesia results in profound hypotension, hypoxemia, or hypercarbia, it is possible that renal and hepatic conditions may worsen.

Airway concerns: Although renal and hepatic patients do not possess any specific airway-related concerns, any parturient undergoing general anesthesia is at slightly increased risk of a hypoxemic or aspiration event. Difficult intubation and postoperative airway obstruction precautions should be taken.

c. Monitored Anesthesia Care

If undergoing a minor procedure, local anesthesia with intravenous sedation may be the most desirable approach.

Benefits: The benefit to intravenous sedation is that it can provide temporary relaxation with very few side effects. If coexisting renal or hepatic disease is present, a minimal amount of short-acting sedation should not further disrupt renal or hepatic physiology. The potential significant changes in postoperative cognition are much less of a concern with intravenous sedation. Airway instrumentation is also avoided.

Drawbacks: The potential drawbacks of this technique are that it may not provide enough relaxation or analgesia for the procedure. Another problem with this technique is that oversedation in a patient with a full stomach status (pregnant with renal or hepatic disease) can result in aspiration.

6. What is the author's preferred method of anesthesia technique and why?

What prophylactic antibiotics should be administered?

Depending on the type of surgery and preexisting allergies, a first-, second-, or third-generation cephalosporin is preferred. In the setting of liver failure and ascites, a third-generation cephalosporin (with increased gram-negative coverage) is preferable.

What do I need to know about the surgical technique to optimize my anesthetic care?

Whether the surgery is obstetric or nonobstetric, the same principles of maintaining renal and hepatic perfusion should be followed.

What can I do intraoperatively to assist the surgeon and optimize patient care?

Preoperative correction of any coagulopathy can make the surgeon’s ability to visualize the operative site much easier. Using Cell Saver blood in a coagulopathic patient may be helpful as it may alleviate some transfusion risks.

What are the most common intraoperative complications and how can they be avoided/treated?

The most common serious intraoperative risk in a patient with known cirrhosis is worsening of their renal function. Preoperative risk factors for renal insufficiency include intra-abdominal surgery and hyperbilirubinemia. Restoration of effective arterial blood volume, medical decompression of the splanchnic circulation, and preservation of renal blood flow can help avoid this complication.

Complications

Cardiac: Worsening of heart failure in the setting of undiagnosed preoperative cirrhotic cardiomyopathy.

Pulmonary: Hypoxemia secondary to the combination of decreased functional residual capacity and hepatopulmonary syndrome.

a. Neurologic:

b. If the patient is intubated, are there any special criteria for extubation?

If the patient possesses significant preoperative encephalopathy, extubation should be performed with caution.

c. Postoperative management

What analgesic modalities can I implement?

If no coagulopathy is present, typical neuraxial techniques for both labor and cesarean delivery are the best choice. If neuraxial techniques are contraindicated because of coagulopathy, short-acting opioids (fentanyl or remifentanil) should be employed. These opioids undergo little to no hepatic metabolism and are therefore safer in cirrhotic patients.

What level bed acuity is appropriate?

Any patient with significant renal or hepatic dysfunction requires a minimum of floor bed with telemetry status. However, if severe encephalopathy is present, step down or ICU is warranted.

What's the Evidence?

Mansour, A, Watson, W, Shayani, V, Pickelman, J. “Abdominal operations in patients with cirrhosis: still a major surgical challenge”. Surgery. vol. 22. 1997. pp. 730-6.

Fitz, JG, Feldman, M, Friedman, LS, Sleisenger, MH. “Hepatic encephalopathy, hepatopulmonary syndromes, hepatorenal syndrome, coagulopathy, and endocrine complications of liver disease”. Sleisenger's and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 2002. pp. 1543-67.

Shaheen, AA. “The outcomes of pregnancy in patients with cirrhosis: a population based study”. Liver Int. vol. 30. 2010. pp. 275-83.

Vidaeff, AC. “Pregnancy in women with renal disease”. Am J Perinatol. vol. 25. 2008. pp. 385-97.

Reid, R. “Liver disease”. Obstetric Anesthesia: Practice and Principles. 2004. pp. 836-45.

Reid, R. “Renal disease”. Obstetric Anesthesia: Practice and Principles. 2004. pp. 904-14. (This focused review summarizes two problems encountered in critically ill pregnant patients: pregnancy-related sepsis and acute renal failure. Common causes and the effects of pregnancy on diagnosis and treatment are discussed.)

Galvagno, S, Camann, W. “Sepsis and acute renal failure in pregnancy”. Anesth Analg. vol. 108. 2009. pp. 572-5. (This review in the "Green Journal's" Clinical Expert Series comes from the Society for Maternal-Fetal Medicine.)

Mastrobattista, JM, Gomez-Lobo, V. “Pregnancy after solid organ transplantation”. Obstet Gynecol. vol. 112. 2008. pp. 919-32.

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