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SPECIAL ARTICLE
Year : 2009  |  Volume : 53  |  Issue : 1  |  Page : 18-29 Table of Contents     

Anticancer Chemotherapy and it's Anaesthetic Implications (Current Concepts)


Professor, Tata Memorial Hospital, Mumbai, India

Date of Web Publication3-Mar-2010

Correspondence Address:
R P Gehdoo
Tata Memorial Hospital, Mumbai
India
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Source of Support: None, Conflict of Interest: None


PMID: 20640073

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Many a times, cancer patients undergo chemotherapy before being subjected for surgery. Such patients pose some serious interactions and complications during the anaesthetic management. So, it is very important to know such interactions, and problems in advance for a smoother and uncomplicated management of anaesthesia. Herewith, a detailed review of this problem is discussed along with the current concepts and solutions.

Keywords: Anticancer chemotherapy drugs, Systemic effects, Implications to anaesthetic management


How to cite this article:
Gehdoo R P. Anticancer Chemotherapy and it's Anaesthetic Implications (Current Concepts). Indian J Anaesth 2009;53:18-29

How to cite this URL:
Gehdoo R P. Anticancer Chemotherapy and it's Anaesthetic Implications (Current Concepts). Indian J Anaesth [serial online] 2009 [cited 2021 Aug 3];53:18-29. Available from: https://www.ijaweb.org/text.asp?2009/53/1/18/60252


   Introduction Top


Cancer is treatable if detected early. Cancer is the second leading cause of death in United States [1] . It is a complex matter having special considerations. Hence, cancer patients deserve special anaesthetic con­siderations. It requires a very close co-operation among surgeon, anaesthesiologist, and referring physician to assure the conduct of surgical procedures on the pa­tient with cancer with maximal safety.

Chemotherapy forms an important aspect of can­cer treatment. With an increased number of patients surviving for a longer period of time, a number of pa­tients, who have received chemotherapy, may be sub­jected to elective and emergency surgery, therefore it is essential to know the effects of the chemotherapeu­tic agents on normal organ systems. The toxicity of can­cer chemotherapy drugs and their relevance to perioperative anaesthesia management relates to the specific agents used, their cumulative dosage, and drug toxicity etc. The most common toxicities to chemothera­peutic agents include cardiac, pulmonary, hematologic, bone marrow, and gastrointestinal effects. Coagulopathies, thrombocytopenia, and anaemia with ulceration and bleeding of the gastrointestinal tract may often occur. [2] .

[Table 1] summarizes various cancer chemotherapy agents, their toxicities, and their relevance to the anaesthesiologist [3] . Of particular importance to the anaesthesiologist in the peri-operative period are the effects of chemotherapeutic agents on the cardio-pul­monary system as well as the other organ systems which is discussed underneath in details.

The effects and problems occurring because of anticancer chemotherapy and it's implications on the anaesthetic management can be discussed under the following headings­

A) Cardiovasculareffects and complications following chemotherapy

B) Pulmonary effects and complications following che­motherapy

C) Other systems affected by chemotherapy (Hepato­renal, CNS, Haemopoetic system)

D) Miscellaneous important complications


   A) Cardiovascular Effects And Complications Fol­lowing Chemotherapy Top


Cancer patients receive a series of chemothera­peutic agents that may adversely affect the heart. [4],[5],[6]

Anthracyclines; i.e. doxorubicin (adriamycin), daunorubicin, and epirubicinare the commonest agents implicated in the development of cardiac toxicity after cancer chemotherapy. Cardiac toxicity can manifest at various times during and following the course of che­motherapy, three types depending on their appearance in relation to timing of therapy, have been identified.

Anthracycline agents may impair myocardial con­tractility. [7] . Similarly, patients receiving mitoxantrone at a total dose of more than 140 mg/m 2 can suffer con­gestive heart failure and anthracycline-induced cardi­omyopathy. Another agent known to cause myocardial tissue injury is cyclophosphamide [8]

A cyclophosphamide dose range of more than 120mg.kg -1 over 2 days can result in severe congestive heart failure and haemorrhagic myocarditis, pericarditis, and necrosis. Patients receiving busulfan in conventional oral daily dosage may suffer endocardial fibrosis, with signs and symptoms of constrictive cardiomyopathy. [9],[10]

Patients with preexisting cardiac disease receiv­ing interferon in conventional doses may have exacer­bations of their underlying illness. More recently, the use of mitomycin for extended periods of time and dos­ages has been shown to produce myocardial damage. [11]

Previous treatment with anthracyclines may en­hance the myocardial depressive effect of anaesthetics even in patients with normal resting cardiac function. [12] The preoperative and anaesthetic assessment of the pa­tients who have received these above mentioned agents may require 2D - echocardiogram or nuclear medicine studies. Such studies permit precise measurement of the left ventricular ejection fraction and detection of regionaland global myocardial dysfunction. Where congestive failure is discovered, the physician will have to treat it preoperatively.

In addition to the above side effects, anthracycline agents can cause dysrhythmias unrelated to the cumu­lative dose. [13]. Such dysrhythmias may occur hours or even days after administration. Commonly observed dysrhythmias include supraventricular tachycardia, complete heart blocks, and ventricular tachycardia. In addition, doxorubicin may prolong the QTinterva1. [14]

In recent years, it has been observed that paclitaxel, when given in combination with cisplatinum, may also produce ventricular tachycardia [15]

Acute and Subacute cardiotoxicity:

It can occur immediately after a single dose or a course of anthracycline therapy. Acutetoxicity com­monly (40%) takes the form of ECG changes such as nonspecific ST-T changes, decreased QRS voltage, and QT prolongation. Decreased R wave amplitude has been thought by some to signal development of chronic cardiomyopathy later, though it is not proved. Sinus tachycardiais the most common rhythm disturbance but avariety of arrhythmias, including ventricular, su­praventricular, and junctional tachycardia, have been reported. Atrioventricular and bundle-branch block have also been seen [16] .

These changes occur at all dose intervals and ex­cept for decreased QRS voltage, resolve 1 to 2 months after cessation of the therapy. Sudden death may also occur, due to ventricular fibrillation. Rare cases of subacute cardiotoxicity resulting in acute failure of the left ventricle, pericarditis or a fatal pericarditis-myocarditis syndrome, particularly in children, have been reported [17] . If these patients recover they should not receive further treatment with anthracyclines. In elderly patients with preexisting heart disease, congestive heart failure can occur, which is generally transient and responds to nor­mal medical management.

Chronic or late cardiotoxicity:

Chronic cardiotoxicity after anthracyclines clas­sically takes the form of cardiomyopathy. CXR review may reveal cardiomegaly. ECG changes occur with these agents and includenon-specific ST-and T-wave changes, prematureatrial and ventricular contractions, sinus tachycardia and low-voltage QRS complexes. [18] Anthracycline cardiotoxicity is a cumulative dose re­lated phenomenon. The incidence of congestive heart failure secondary to anthracycline induced cardiotoxicity increases with dose. Praga et al [19] re­ported that an average incidence of 7% at 550 mg/m 2 , 15% at 600 mg/m 2 , and 35% at 700 mg/m 2 . At total doses [20] less than 400 mg/m 2 the incidence of CHF is 0.14%. The rapid increasein incidence of CHF after a dose of 550 mg/m 2 has made it a popular empiric-lim­iting dose for doxorubicin-induced cardiotoxicity.

Late onset cardiotoxicity:

Several recent studies, extensively reviewed elsewhere [21] have reported occultventricular dysfunc­tion, heart failure and arrhythmias occurring in previ­ously asymptomatic patients more than a year after anthracycline therapy. [22],[23] . It is postulated that doxoru­bicin can cause subclinical myocardial injury during pre­adolescent years and this in later years retards appro­priate growth of the myocardium during growth spurt.

Pathogenesis ofanthracycline cardiotoxicity:

The anthracycline antibiotics react with cyto­chrome P-450 reductase in the presence of reduced nicotinamide adenine dinucleotide phosphateto form semiquinone radical intermediates, which in turn can react with oxygen to form superoxide anion radicals. These can generate both hydrogen peroxide and hy­droxylradicals, which are highly destructive to cells thus causing myofibrillarlysis, cytoplasmic vacuolization, and degeneration of nuclei and mitochondria in the myocytes. Severe myocyte damage results in decreased myocardial contractility and CHF.

Risk factors for development of anthracycline cardiotoxicity:

Apart from the total dose, patients who have received high dose radiation to the mediastinum and those who are on concurrent cyclophosphamide therapy are particularly susceptible to this cardiomyopathy. The other risk factors are extremes of age, prior is chaemic heart disease, hypertension, valvular heart disease and liver diseases.The risk involved at a cumulative dose in the range of 300-450 mg/m 2 is about 1-10%, while doses higher than this invites a riskof >30%.

Investigations for the detection of anthracycline cardiotoxicity:

The best currently available noninvasive method for assessing cardiac function is radionucleide angio­cardiography. The commonly studied parameters with radionucleidestudies are left ventricular ejection frac­tion (LVEF). A decrease in LVEF to less than 45% is considered to indicate anthracycline-induced cardiotoxicity. 2-Dechocardiography is a non-invasive method of cardiac valuation. Diastolic dysfunction on echocardiogram may represent an earlier manifestation of anthracycline toxicity. The newer noninvasive meth­ods to know the actual myocardiald amage are by us­ing imaging with monoclonalindium-111-antimyosin antibodies. These antibodies bind to the exposed myosin in the necrosed myocardial cells. A diffuse up take on imaging indicates a generalised process such as anthracycline cardiomyopathy; a focal uptake will sug­gest local pathology such as myocardialinfarct. [24]

Other chemotherapeutic agents also have adverse cardiac effects, which are important for the anaesthe­tist to know. [Table 2] summarizes them as follows:-

Problems with anaesthesia management:­

An appropriate anaesthetic plan including the in­vasive monitoring techniques hinges on thorough pre­operative assessment. Invasive arterial blood pressure recordings and apulmonary artery catheterization may be necessary if significant myocardial impairment is present. Anthracycline treated patients under anaesthe­sia can develop acute intraoperative left ventricular fail­ure refractory to â- adrenergic receptor agonists. Amrinone and sulmazole are the new class of cardiotonics with inotropic drugs useful in such conditions.


   B) Pulmonary Effects And Complications Of Cancer Chemotherapy Top


Cancer patients commonly suffer pulmonary com­plications. 75% to 90% of pulmonary complications are secondary to infection. The cancer patient can suf­fer infectious complications secondary to chemotherapy (e.g.,Bleomycin), thoracic radiation, and multiple pul­monary resections. [25]

Pulmonary complications are a significant prob­lem; respiratory failure in cancer patients requiring as­sisted mechanical ventilation is associated with a 75% mortality rate. [26],[27],[28] In patients with systemic cancer, the differential diagnosis of pulmonary infiltrates seen on a routine chest radiograph is extensive; there are many causes for such infiltrates. [29],[30],[31]

Administration of several chemotherapeutic agents, such as busulfan, cyclophosphamide, paclitaxel, etc, can lead to pulmonary complications. Bleomycin, an antitumour agent, is the foremost of these in pro­ducing lung damage.

Several patterns of pulmonary toxicity produced by bleomycin have been described:

  1. Dose dependent interstitial pneumonitis progressing to chronic fibrosis
  2. An acute hypersensitivity pneumonitis with periph­eral eosinophilia resembling eosinophilic pneumonia.
  3. An acute chest pain syndrome.
  4. A bronchitis obliterans with organising pneumonia.
  5. Pulmonary veno-occlusive disease.


About 0-40% patients are reported [32] to de­velop pulmonary toxicity, 11-30% patients will have non-lethal pulmonary fibrosis and the mortality associ­ated with bleomycin toxicity will range from 2-10%. Progressive interstitial pneumonitis and fibrosis is the most common pattern of bleomycin lung injury. Symp­toms generally occur between 4 to 10 weeks after bleomycin therapy, however in about 20% patients with radiographic and histological features of bleomycin toxicitymay be present without any clinical symptoms. The risk factors for bleomycin pulmonary toxicity are old age, acumulative dose >400-450 U, poor pulmonary reserves, radiotherapy, uraemia, higher inspired oxy­gen concentrations, and concomitantly administered other anticancer drugs.

Mechanisms of pulmonary toxicity:

Though the threshold dose level for the develop­ment of pulmonary disease is in the range of 400 to 450mg, fatal pulmonary fibrosis has been reported with doses as low as 50mg. The mechanism of pulmonary toxicity as­sociated with the use of bleomycin, is probably due to direct cytotoxicity and in patients receiving bleomycin, type I pneumocytes are replaced by type II pneumocytes. Continued exposure to bleomycin prevents reversion of type II to type I pneumocytes and further leads to meta­plasia of the type II cells to cuboidal epithelium. Further exposure prevents effective repair and fibrosblasts and macrophages migrate into the interstitium and the alveoli. Ultimately pulmonary fibrosis results. One proposed mechanism for bleomycin toxicity involves the production of superoxide and other free radical moieties, which then cleave nuclear DNA. The production of these highly oxi­dizing radicals might be increased by the inspiration of for­tified concentrations of oxygen.

Clinical presentation:

The lesions seen frequently are in the lower lobes and sub pleural areas and chest X-ray shows bilateral basal and peri-hilar infiltrates with fibrosis. The first signs and symptoms of toxicity are fever, cough, dyspnoea and bibasilar rhonchi and rales, which may progress to exertional dyspnoea with mild X-ray changes and a normal resting PaO 2 or a severe form of hypoxia at rest. The earliest detection of pulmonary fi­brosis may be achieved through the serial evaluation of pulmonary function. Sequential measurement of car­bon monoxide diffusion capacity (DLCO) may indi­cate the presence of occult pulmonary changes. Arte­rial hypoxemia is commonly found and spirometry re­veals decreased lung volumes compatible with restric­tive lung disease. Regression or amelioration of the toxic pulmonary pathology may occur with immediate ces­sation of therapy. Steroid therapy has been found to be effective in some cases.

Occasionally, it may manifest itself as noncardiogenic pulmonary edema, chronic pneumoni­tis and fibrosis, and hypersensitivity pneumonitis. [33]

Hyperoxia & Bleomycin:

Of utmost importance to the anaesthesiologist is the debate about the amount of oxygen to be admin­istered to a patient coming up for surgery after being given bleomycin. The debate was sparkedoff by a land­mark report by Goldiner etal [34] . They described 5 pa­tients undergoing surgery after receiving bleomycin, given >39% oxygen intraoperatively, developed ARDS and died. Subsequent 13 patients, given > 25% oxy­gen, survived the surgery without pulmonary complications [35] . This need to restrict inspired oxygen con­centration was subsequently questioned by La Mantia et al, who reported a series of 16 patients with uncom­plicated perioperative period in spite of receiving high FiO 2 (>0.41) intraoperatively [36]

A recent study by Donat et al [37] evaluating 77 patients undergoing 97 extensive resection procedures after receiving bleomycin seems to have solved the is­sue. They found that, though the in spired concentration of oxygen was > 40%, and 25% patients did develop minor pulmonary complications;none of them devel­oped ARDS or died. The authors concluded that perioperative oxygen restriction is not necessary and a meticulous perioperative fluid balance including trans­fusions as a significant predictor of postoperative pul­monary morbidity. They also noted that the duration of surgery and post-chemotherapy forced vital capacity are significant predictive factors of procedure related pulmonary morbidity. On the basis of available data it seems prudent to reduce the concentration of inspired oxygen to the lowest level to maintain SpO 2 > 90%. Intraoperative monitoring is the key to safe administra­tion of oxygen to these patients. Arterial blood gas analysis should be performed by an indwelling arterial cannula or intermittent sampling. The judicious use of intraoperative PEEP to enhance oxygenation and the postoperative use of rigorous physiotherapy to treat ventilation-perfusion abnormalities may be preferable to the use of enriched oxygen concentrations. Fluid balance is another important factor in predicting pul­monary morbidityin-patients receiving bleomycin. Con­servative fluid management is important; use of colloids is beneficial as compared to crystalloid.

Other chemotherapeutic agents also have adverse pulmonary effects, which are very vital for the anesthe­tist to understand. [Table 3] summarizes them as follows:-


   C) Effects Of Cancer Chemotherapy Agents On Hepato-renal, And CNS System Top


i) Renal complications :­

Cisplatinum , a commonly used anticancer drug has been found to produce toxic effects like nephrotoxicity, myelosuppression, neuropathy in stocking and glove distribution, auditory and visual impair­ment. The dose-limiting factor for single agent use, however, is nephrotoxicity. 30% of patients receiv­ing cisplatinum will develop nephrotoxicity, especially if the hydration is not properly controlled. It causes coagulation necrosis of proximal and distal renal tu­bular epithelial cells and in the collecting ducts lead­ing to are duction in the renal blood flow and glom­erular filtration rate (GFR). Cisplatinum leads to wasting of magnesium and potassium. A single dose of 2mg/kg or 50-75mg/m 2 will produce nephrotox­icity in 25-30% of patients [38] .

Acute renal failure can result within 24 hours of administration of a single dose of cisplatinum. The long-term effects were reported by Fjeldberg et al [39] who found a 12.5% reduction of GFR after 16 to 52 months after administration of cisplatinum. Proper hydration with forced dieresis seems to decrease the incidence of renal toxicity by reducing the concentration of cisplatinum in renal tubules and the amount of time it remains in contact with renal tubules. Use of normal saline is particularly beneficial as high chlo­ride concentrations in the tubules inhibit the hydroly­sis of cisplatinum. The renal toxicity may be accen­tuated if the patient receives aminoglycosides concomi­tantly. The newer analogues of cisplatinum, such as carboplatinum and oxaloplatinum are less nephrotoxic with equal efficacy in controlling the malignancy.

Methotrexate causes the acute nephrotoxicity as a result of its intratubular precipitation [40] .

Other chemotherapeutic agents also have adverse renal effects are summarized in the [Table 4] as follows:­

ii) CNS complications:­

Vinca alkaloids were the first anticancer drugs found to have neurotoxiceffects. Vincristine is prob­ably the only drug whose dose limiting toxicityis neu­rotoxicity. It can affect the central, peripheral or the autonomicnervous systems. Peripheral neuropathies present as peripheral paresthesias with depression of deep tendon reflexes. The paresthesias progress proxi­mally with therapy. Motor dysfunction and gait disor­ders can occur. Vincristine, [41] vinblastine, procarbazine, cisplatinum [42] all can cause a toxic neuropathy with paresthesia, loss of deep tendon reflexes and muscle weakness.

Autonomic neuropathy with orthostatic hypoten­sion is a rare concomitant of neoplasia [43] . Cranial nerve effects may manifest as opthalmoplegia and facial palsy. Autonomic neuropathy can present asorthostatic hy­potension, erectile dysfunction, constipation, difficulty in micturition, bladder atony, etc.

Cisplatinum , along with its effects on the kidney also affects the nervous system. 50% patients receiving cisplatinum will display neurotoxicity depending on dose and treatment duration. It generally takes the form of paresthesias. Continued treatment will lead to loss of deep tendon reflexes, vibration sense and sensory ataxia.

As far as regional anaesthesia is concerned, one should be aware that in a considerable percentage of patients a sub-clinical, unrecognized neuropathy may be present in patients with previous cisplatinum che­motherapy. Recently, a diffuse brachial plexopathy af­ter interscalene blockade has been reported in a pa­tient receiving cisplatinum chemotherapy. Thus, if re­gional anaesthesia is contemplated, a detailed pre-op­erative neurological examination and careful assessment of the risks and benefits is warranted. [44]

Other chemotherapeutic agents also have adverse CNS effects are enumerated in the [Table 5] as follows:­

iii) Hepatic complications :­

Hepatocellular dysfunction is manifested as raised serum enzymes, fatty infiltration of liver and cholestasis, due to direct toxiceffect ofthe drug or it's metabolite. L-asparginase and cytarabine are most commonly implicated agents in hepatocellular dysfunc­tion. A decreased synthetic function with low proteins and coagulation abnormalities may be seen. Ascites, painful hepatomegaly, and encephalopathy may result after administration of cytarabine, cyclophosphamide, mitomycin, etc.


   D) Miscellaneous Adverse Effects Of Cancer Che­motherapy Agents Top


i) Haematological complications:- Bone mar­row function in cancer patients may be disturbed by primary bone marrow disorders (e.g.,leukemia), bony metastases (e.g., from breast cancer), as well as myelosuppressive chemotherapy. The production of any or all blood elements may be impaired. There is dys­functional coagulation. The PTand PTTare shortened. There is increase in factor I, V, VIII, IX, XI and FDP. There is reduced survival of the platelets and the de­creased antithrombin III activity. There are no prospec­tive trials to date that establish the minimal platelet count necessary to prevent bleeding with specific procedures. Some investigators have maintained a minimal level of 50,000 platelets per microliter in the intraoperative and postoperative period. Correction of other coagulation disturbances is important before undertaking surgical intervention in the thrombocytopenic patient. In view of these findings, a close cooperation among the sur­geon, anaesthesiologist, and hematologistis required for optimal management and maximal safety. [45]

Myelo-suppression caused by all the chemothera­peutic agents is partially or completely reversible within 1 to 6 weeks of termination of therapy.

ii) Syndrome of inappropriate antidiuretic hor­mone secretion (SIADH):­

Another metabolic abnormality in patients with cancer like lung, pancreas-adeno-carcinoma, duode­num, thymoma, mesothelioma, leukaemia, hodgkin, reticulum cell sarcoma, is SIADH, which occurs in 1% to2% of cancer patients.

Some drugs, such as vasopressin, carbamazepine, oxytocin, vincristine, vinblastine, cyclophosphamide, phenothizianes, tricyclic antidepressant agents, narcot­ics, and monoamine oxidase inhibitors, can also induce SIADH. [46]

iii) Steroid administration:

The oncology patient often has a history of exog­enous glucocorticoid administration as part of a che­motherapy regimen. The physician at the time of pre­operative evaluation has to decide on the use and the amount of stresss teroid coverage. The patient who has received ≥2 weeks of glucocorticoids within the past year is considered at risk for adrenal suppression. How­ever, many of these patients are capable of a normal stress response. The corticotrophin (ACTH) stimulation test is the definitive test to identify adrenal sup­pression.

iv) Tumorlysis syndrome:­

Another frequently seen complication in cancer patients is the tumorlysis syndrome. [47] Chemotherapy induces rapid tumor cell lysis in patients with a large malignant cell burden over an exquisitely sensitive tu­mor [48],[49] This classically occurs in patients with Burkitt's lymphoma, non-Hodgkin's lymphomas, acute lympho­blastic and nonlymphoblastic leukemias, and chronic myelogenous leukemia. In addition, it may also occur continuously in patients with lymphomas and leukemia following treatment with chemotherapy, radiation, glu­cocorticoids, tamoxifen, or interferon. The clinical mani­festations of this syndrome are related to the metabolic abnormalities.

In those patients with suspected tumorlysis syn­drome or for those patients who receive chemothera­peutic agents likely to induce the syndrome, prevention is the mainstay of treatment. To prevent the develop­ment of acute renal failure, patients who are to undergo treatment for malignancies should receive vigorous in­travenous hydration, often with diuretics or renal doses of dopamine to ensure adequate urine output.

v) Chemotherapy and wound healing:­

The outcome of surgical procedures may be affected by the wound-healing impairment caused by antineoplastic agents used to treat the underlying tu­mor. The neutropenia that accompanies some chemo­therapy within 7 to 10 days of administration can inter­fere with the early phases of wound healing. Most pa­tients with WBC count 500/mm 3 have no adverse ef­fects of leukopenia on surgical wound healing. Chronic anemia also has little effect on surgical wound healing [50] .

The effects of chemotherapy directly on wound healing depend on doseand the timing of drug admin­istration relative to creation of the wound. A high inci­dence of wound complications has been reported in women undergoing mastectomy after receiving preop­erative chemotherapy and radiation. Bleomycin has not been associated with increased wound complications.

Anaesthetic considerations for patients after che­motherapy

The interaction between an anaesthesiologist and a cancer patient starts with a preoperative visit for a surgical procedure. The goals of such a preoperative visit would be as follows:­

  • To optimize patient's physical status.
  • To assess effects of cancer and cancer therapies (che­motherapy, radiotherapy and surgery) on patient.
Some of the important features and care before planning anaesthesia in such a chemotherapy received patient are as follows -

• In pre-anaesthetic checkup, one must obtain a pertinent, comprehensive past medical history, pre-existing condition prior to surgery and anaesthesia, medi­cations, allergies, family history and a complete sys­temic examination. The anaesthesiologist's role in pre-­operative evaluation and preparation of the surgical patient and intraoperative and postoperative manage­ment is of great importance. This begins with a thor­ough history and physical examination.

• Routine clinical tests like complete blood count, urine analysis, serum electrolytes, fasting blood sugar, serum BUN, pulmonary function tests, PaO 2 and PaCO 2 contentsby arterial blood gas analysis, serum osmolality, bilirubin, creatinine, amylase, liver function tests, chest X-ray and ECGare mandatory. [51] Aware­ness of the side effects of the various chemotherapeu­tic agents enables other appropriate investigations to be carried out and institution of corrective measures when possible will ensure a well-prepared patient.

• Immuno-suppresion occurs with the use of all the alkylating agents. Meticulous attention must be given to aseptic techniques in the perioperative period in or­der to avoid potentially lethaliatrogenic infection.

• Pneumonitis and pulmonary fibrosis may be induced by many of the chemotherapeutic agents. His­tory or symptoms suggestive of exertional dyspnea or dyspnea at rest should alert the physician to this prob­lem. In addition to chest X-ray, arterial blood gases are necessary. Pulmonary function tests including arte­rial blood gas, spirometry, and carbon monoxide dif­fusing capacity should be evaluated. Findings compat­ible with interstitial fibrosis include increased alveolararterial gradient, restrictive lung disease, and decreased carbon monoxide diffusing capacity. [52] Patients who had a bleomycin therapy should not receive high inspired oxygen concentrations and that colloid rather than crys­talloid replacement should be preferred both during and after surgery. Ventilator support should be anticipated in the postoperative period.

• Cardiotoxicity may occur in-patients who have received anthracyclines. The ECG may reveal diminu­tion of the QRS voltage, systolictimed intervalmay be increased, and ejection fraction as well as fractional shortening may be decreased. Congestive heart failure is treated using diuretics, digitalis and oxygen. Operat­ing and recovery room monitoring should include ECG, urinary output, central venous pressure and when fea­sible pulmonary arterial and wedge pressures. Huetteman and colleagues [12] showed that previous treat­ment with anthracycline might enhance the myocardial depressant effects of anaesthetics even in individuals with healthy cardiac function at rest.

• Hepatotoxicity may occur with the use of most of the anticancer drugs. Anaesthetic drugs incriminated, as causing liver damage should not be administered. Busulfan, methotrexate, cisplatinum and others may cause nephrotoxicity. Balanced electrolyte solutions started the evening before surgery will aid in maintain­ing optimal renal flow and glomerular filtration. Poten­tially nephrotoxic drugs should be avoided.

• The effects of cyclophosphamide, a pseudo­cholinesterase inhibitor, could last for 3-4 weeks from the end of its use, and Zsigmond and Robins [53] argued that this occurrence might justify or explain the recognised hazard because of the drug's interaction with suxamethonium (a depolarising muscle relaxant, metabolised by pseudocholinesterase), inducing a risk of protracted postoperative apnoea.

• Negative interactions between methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) are well known. Although the mechanism of this inter­action is not completely clear, NSAIDS are known to reduce the excretion of methotrexate. A competition for receptor sites at renal tubular excretion has been postulated but the mechanism is not yet understood; this interaction might resultin potentially fatal side-ef­fects for patients. [54]

• Central and autonomic nervous system toxic­ity and peripheral neuropathies occur with vincristine, cisplatinum and others. Therefore regional anaesthesia is contraindicated. The preoperative state of sensorium and neurologic deficits should be documented. Anti-cholinesterase effects of alkylating agents are signifi­cant. Reduction of dosage of succinylcholine is indicated to prevent prolonged respiratory depression. Monoamine oxidase like inhibition may occur with the administration of procarbazine. Because of synergistic action barbiturates, antihistaminic, phenothiazines, nar­cotics and tricyclic antidepressants should be used with caution. Diarrhea is a side effect of many of the anti­cancer drugs. Attendant serum electrolyte and fluid abnormalities should be corrected before surgery and also in the postoperative period.

The cancer patient like any other high risk pa­tients requiring anaesthesia deserves a special care and considerations. A growing number of patients undergo surgical procedures with general anaesthesia soon af­ter receiving chemotherapy; occasionally such treatment can be given during surgery.Therefore, it is worthwhile and prudent to understand the pathophysiology of can­cer and consider the pharmacological interactions be­tween anticancer and anaesthetic drugs. Anti-cancer chemotherapeutic drugs may cause generalized and specific organ toxicities and may also give rise to vari­ous unpredictable or life-threatening peri-operative complications, rendering a detailed pre-operative as­sessment of patients with previous chemotherapy man­datory. Thus, special consideration and understanding of the cancer patient's anaesthesia-related needs will result in superior patient care and outcomes.



 
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