intravenous hyperalimentation in patients with head and neck cancer

INTRAVENOUS HYPERALIMENTATION IN PATIENTS WITH HEAD AND NECK CANCER

EDWARD M. COPELAND, MD,* BRUCE V. MACFADYEN, JR, MD,+ WILLIAM S. MACCOMB, M D , ~

OSCAR GUILLAMONDEGUI, MD,§ RICHARD H. JESSE, MD, I t AND STANLEY J . DUDRICK, MD**

Intravenous hyperalimentation was utilized to support nutritionally 23 malnourished patients with major head and neck tumors during surgical treatment, radiotherapy, or the convalescent period. Fifteen patients were treated during the perioperative period and 12 survived. Six patients received convalescent nutritional support successfully 4 to 24 months following operation or radiation treatment. Two patients received treatment with hyperalimentation throughout a protracted course of radiation therapy. Weight gain, wound healing, and recovery were achieved in all but 3 patients. Subclavian vein thrombosis occurred in 1 patient, and catheter-related sepsis occurred in 2 patients. Otherwise, hyperalimentation was safe and efficacious in the debilitated patients. These patients may now become acceptable risks for surgical treatment or radiation therapy by nutritional repletion with intravenous hyperalimentation.

Cancer 35:606-611, 1975.

H E COMMON DENOMINATOR OF T H E MULTIPLE T complications which ultimately cause death in patients with major head and neck tumors is malnutrition. Although the malignant lesion may be anatomically resectable, negative nitrogen balance, inanition, and im- paired capacity for wound healing often eliminate these patients as candidates for surgical treatment or radiotherapy, because oral nutrition and/or nasogastric tube feeding with various blenderized diets will not meet their nutritional needs. At times, an oropharyngeal lesion is so large that a nasogastric tube cannot be inserted; moreover, protein-depleted patients cannot assimilate a major portion of the administered diet because of malabsorption with resultant nausea, vomiting, and diarrhea. Since the advent of intravenous hyperalimenta-

Presented at the 27th Annual hleeting of The James Ew- ing Society, Maui. HI, April 8-13, 1974.

From the University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute and The Lniversity of Texas Medical School at Houston, T X .

Supported in part by Grant Ca 05831-13 from the National Institutes of Health.

* Associate Professor of Surgery. ' Assistant Professor of Surgery.

4 Professor of Surgery. s Assistant Professor of Surgery. ' I Professor of Surgery ** Professor and Director, .Program in Surgery. Address for reprints: Dr Edward M. Copeland, Program

in Surgery, The University of Texas Medical School at Houston, 6400 West Cullen Street, Houston, TX 77025.

Received for publication July 5, 1974.

t10n,~v~ vitamins, minerals, amino acids, and caloric sources can be provided parenterally in amounts necessary to correct negative nitrogen balance and to maintain the critically ill patient in an anabolic state. Intravenous hyperalimentation (2500 to 3000 kcal/day) has recently been utilized at our institution for nutritional support in those patients with head and neck tumors who were intolerant of nasogastric tube feedings, or who, because of cachexia, were poor risks for any form of oncologic therapy.

MATERIALS AND METHODS

Each of 23 patients (Table 1) treated with intravenous hyperalimentation (IVH) had lost body mass to at least 20 pounds below his ideal or usual body weight, and had a serum albumin concentration of less than 3 g/100 ml. The hyperalimentation solution was administered via a catheter inserted percutaneously into the subclavian vein on the side contralateral to any known cervical lymph node metastasis. Sterility of the intravenous solution and delivery system was maintained by rigorous adherence to pre- viously outlined aseptic and antiseptic tech- niques.2 The same registered nurse, assigned to the hyperalimentation team, assisted with the insertion of each catheter, and changed the catheterization site dressings and intravenous connecting tubing regularly. In those patients with pharyngocutaneous and/or tracheostomy stomas, a sterile plastic sheet was placed over

606

No. 3 HYPERALIMENTATION I N CANCER Copeland et al. 607

TABLE 1 . Hyperalimentation and Head and Neck Malignancies

Reason for IVH No. patients

Perioperative support Convalescent support Radiation

TOTAL

15 6 2

23

the catheter dressing to minimize the risk of con- tamination from stoma1 secretions. The catheter skin entry site was placed outside the radiated field in those patients who received radiation therapy. The hypertonic dextrose and amino acid solutions were prepared under filtered-air, laminar-flow hoods by trained pharmacists. No additions were made to the nutrient solutions after the bottles left the pharmacy. The integ- rity of the hyperalimentation delivery system was not violated for administration of blood products, injection of bolus medication, mea- surement of central venous pressure, or with- drawal of blood samples.

At the termination of hyperalimentation therapy, each catheter was removed aseptically, and the most distal 2-inch long segment of catheter was cultured for fungi and bacteria. A clinical data sheet listing body weight, vital signs, antibiotics administered, complications, sources of infection, radiation therapy, surgical procedures, and cause of death was maintained daily on each patient. A metabolic scale was used to weigh all patients. Following the initial period of rehydration, weight gain of more than 1.5 pounds per day was considered secondary to fluid retention, and a diuretic was administered. Hypoproteinemia was initially corrected with intravenous serum albumin, and hemoglobin concentration was restored to normal levels by the administration of packed red blood cells.

RESULTS

Perioperative

Of 15 surgical patients in this series, laryngopharyngectomy was performed in 12, 9 of whom had simultaneous radical neck dissection and thoracoacromial flap repair. Glossec- tomy, mandibulectomy, and neck dissection were performed in 3 patients. Intraoral reconstruction with a forehead flap was utilized in 1 patient (Table 2). Radical resection of a large volume of malignant primary tumor was necessary in all 15 patients, and radical neck

TABLE 2. Perioperative Support

Operation No. patients

Laryngopharyngectomy 12 Radical neck dissection 12 Thoracoacromial flap 9 (1 bilateral) Glossectomy 3 Mandibulectomy 3 Forehead flap 1

dissection was necessary in 12 patients to remove gross metastatic disease (Table 3). For example, in 5 patients, squamous cell carcinoma involved an entire piriform sinus and the lateral pharyngeal wall. In 1 patient, the piriform sinus lesion was continuous with malignant disease invading the overlying skin.

Hyperalimentation was utilized in these patients for an average of 44.2 days, and was successful in promoting an average weight gain of 13.5 pounds. Eight patients were placed on IVH preoperatively for an average of 17.4 days, and required intravenous nutritional support for an average of 23 days postoperatively. In 7 patients IVH was not used preoperatively, but was begun in the immediate postoperative period. These patients required intravenous nutritional support postoperatively for an average of 48.5 days until nutrition could be maintained ade- quately by the enteral route. In 3 patients who received IVH postoperatively, the major indica- tion was the development of an esoph- agocutaneous fistula, 2 of which closed spontaneously within 20 days of initiation of therapy. The third fistula was closed surgically following 38 days of intravenous nutritional support.

Of the 19 subclavian feeding catheters utilized in these 15 patients, 5 (26.3%) grew organisms when cultured (Table 4). In 2 patients, the same organism was cultured from the blood stream and the catheter simultaneously. The other 3

TABLE 3. Anatomical Location of Lesion in Patients Receiving IVH for Perioperative Support

Location

Piriform sinus Epiglottis and vallecula Alveolar ridge Tongue Posterior pharyngeal wall Larynx Submaxillary gland Hypopharynx Cervical esophagus

Postradiation No. patients (no. patients)

5 1 2 1 1 1 1 2 1 1 1 1

608 CANCER March 1975 V O l . 35

TABLE 4. Positive Catheter Cultures in Perioperative Parients

Organism No. of Catheters

Candida tropicalis Candida albicans Serratia marcescens Klebsiella pneumoniae

TVTAL

2* I * 1 1 5

* Same organism cultured from blood and catheter in two patients.

positive catheter cultures were incidental and were not associated with any evidence of clinical sepsis. Subclavian vein thrombosis occurred in 1 patient but resolved spontaneously and promptly after the removal of the subclavian catheter.

Death occurred in three patients. In one patient, separate squamous cell carcinomas involved the vallecula, epiglottis, and left alveolar ridge. He underwent laryngopharyngectomy, total glossectomy, left radical neck dissection, hemimandibulectomy, and repair with a thoracoacromial flap. Although this 74-year-old man gained 15 pounds during 52 days of IVH, the limits of wound healing capacity apparently were exceeded by the anatomical resection of the three primary cancers. The second patient, who had squamous cell carcinoma of the piriform sinus, underwent laryngopharyngectomy, right radical neck dissection, and repair with a thoracoacromial flap. Hyperalimentation was begun in the postoperative period when the wound became infected and dehisced. Wound healing with generation of healthy granulation tissue occurred quite rapidly, and the patient underwent a series of reconstructive procedures to cover the skin defect. The patient died 104 days following the initiation of IVH. The cause of death was aspiration pneumonia. The patient had vomited intragastric contents via his pharyngostomy stoma and had aspirated them into his tracheostomy stoma. The third patient had a squamous cell carcinoma involving the larynx and vallecula and underwent laryngopharyngectomy, right and left radical neck dissection, and reconstruction with a thoracoacromial flap. Wound suppuration and rupture occurred in the immediate postoperative period, and intravenous hyperalimentation was begun. The patient developed bilateral lower lobe pneumonia, and Candida albicans was cultured from his sputum and blood. The patient had been treated with multiple combinations of antibiotics throughout the postoperative period. The

subclavian catheter was removed, and Candida albicans was cultured from its tip. The patient died of respiratory failure and sepsis, secondary to extensive bronchopneumonia.

Clinical Example 1

B.Z. is a 55-year-old Latin American male who was admitted to the hospital on October 1, 1973. During the previous 3 months, he had experienced increasing dysphagia, a 25-pound weight loss, and a rapidly growing mass lesion on the right side of his neck. O n physical ex- amination, a 4 X 5 cm fixed mass was noted in the midjugular region of the right neck. O n mirror laryngoscopy, an ulcerated infiltrating lesion was noted to involve the entire right hypopharynx, piriform sinus, and postcricoid area of the larynx. The superior margin of the mass ex- tended to the inferior pole of the right tonsil. The patient’s admission weight was 131 pounds; serum albumin was 2.1 g/100 ml. Intravenous hyperalimentation was begun preo eratively.

the patient underwent laryngopharyngectomy, cervical esophagectomy, right radical neck dissection, and left modified neck dissection. Pri- mary wound closure was obtained with a deltopectoral flap, and a pharyngostomy, esoph- agostomy, and tracheostomy were fashioned. Intravenous hyperalimentation was resumed on October 12 and was continued until the patient could tolerate nasogastric tube feedings. When IVH was discontinued on Novem- ber 5, 1973, the patient weighed 147 pounds, and all wounds had healed primarily without complications. Intravenous nutritional support was not necessary for the remainder of the patient’s hospitalization. O n November 20, 1973, a delayed flap was created for reconstruction and closure of the pharyngostomy and esoph- agostomy stomas. The final step to complete this procedure was carried out on December 12, 1973, and shortly thereafter, the patient was discharged from the hospital swallowing liquids and soft foods.

Nine days later, after a weight gain o P 3 pounds,

Clinical Example 2

In 1968, E.H. was treated by partial glossectomy for a Grade I1 squamous cell carcinoma of the tongue. She was healthy until January, 1973, when a right subdigastric lymph node metastasis was identified. She underwent a right radical neck dissection and had an uneventful postoperative course. In February, 1973, a 1 cm in diameter squamous cell carcinoma was identified on the posterior lateral pharyngeal wall at the level of the tip of the epiglottis. This lesion was resected through a midline jaw and tongue splitting approach, and a partial-thickness skin

No. 3 HYPERALIMENTATION I N CANCER Copeland et al. 609

graft was applied to the posterior pharyngeal wall. Her weight upon admission to the hospital in February was 110 pounds. Her serum albumin was 4.2 g/100 ml. Posto eratively, the patient’s swallowing reflex was &pressed, and attempts at oral alimentation were ac- companied by regurgitation. The patient developed bilateral lower lobe pneumonia and was maintained nutritionally with 5% dextrose solutions administered intravenously. O n the 25th postoperative day, a nasogastric feeding tube was inserted, but any attempt to feed a blenderized diet produced diarrhea, bloating, and crampy abdominal pain. The intravenous hyperalimentation service was consulted on the 42nd postoperative day, at which time the patient was passing approximately 20 liquid stools per day in response to nasogastric feedings con- sisting primarily of skimmed milk. She was semicomatose, dehydrated, and weighed 97 pounds. All intragastric feedings were stopped, and the patient was placed on IVH. The diarrhea ceased immediately thereafter. Over the ensuing 48 days, she gained 26 pounds in weight, and her gag and swallowing reflexes returned to normal. When oral alimentation was reinstituted, bowel movements became formed and occurred only once or twice per day.

Convalescent Support

Six patients were admitted to the hospital for nutritional supportive care 4 to 24 months following operation or radiation treatment (Table 5). Hyperalimentation therapy was utilized for an average of 26.6 days, and the patients achieved an average weight gain of 10.5 pounds. One patient who received radiation therapy for laryngeal carcinoma developed a tra- cheocutaneous fistula and a mediastinal abscess. Following 35 days of IVH, the fistula healed, and the abscess resolved. Four of the patients eventually were discharged from the hospital on nasogastric tube feeding regimens, and two other patients required gastrostomy feeding for their long-term ambulatory nutritional maintenance.

Radiation Therapy

Two patients were supported with IVH throughout a protracted course of radiation therapy, without complications. One patient, a 22-year-old man, had a large squamous cell carcinoma of the nasopharynx with bilateral cervical lymph node metastases. O n admission to the hospital he was unable to stand un- supported, and he weighed 82 pounds. During the next 86 days, he received a total dose of 6000

TABLE 5. Convalescent Support

Reason for IVH (1 patient each)

Time following therapy (mo.)

Postradiation, nasopharynx 4 Pastradiation, tongue and neck 6 Postradiation, tonsil and neck 4 Cryosurgery (gingiva), radical 1 1

neck dissection

postlaryngopharyngectomy Esophageal stricture 12

Postradiation, larynx and neck 24

rads to the nasopharynx and both lower neck portals. During this time, he gained 17 pounds in weight and experienced minimal mucositis secondary to the radiation treatment. At the end of the course of treatment, complete clinical regression of the primary cancer and the neck node metastases had occurred. The second patient, a 57-year-old man, had a squamous cell carcinoma of the supraglottic larynx and was treated with fast neutrons to a 6500 rad cobalt- 60 equivalent dose directed at the epiglottis, base of the tongue, and larynx. At the outset of therapy, the patient experienced extreme mucositis and was unable to tolerate oral feedings or a nasogastric feeding tube. Nutritional maintenance with IVH for the next 91 days al- lowed the patient to heal the radiation pharyngitis, maintain his strength and morale, and gain 13 pounds during treatment.

DISCUSSION

Intravenous hyperalimentation was safe and efficacious in this population of patients who were incapable of adequate gastrointestinal assimilation of required nutrients. Weight gain, wound healing, and recovery were achieved in all but three patients. Without intravenous nutritional support, these patients might have been denied possible curative surgical treatment or radiotherapy because of the physician’s fear of potential complications secondary to malnutrition.

The majority of patients with head and neck cancers smoke, consume ethyl alcohol, have poor oral hygiene, and are malnourished. The surgeon or radiotherapist who treats these patients must attempt to prepare the patient psy- chologically and physiologically for the recommended antitumor treatment. Dietary counseling and vitamin supplementation may help in the nutritional rehabilitation of most of these patients prior to therapy. Other patients may require admission to the hospital for naso-

6 10 CANCER March 1975 VOl. 35

gastric feeding tube supplementation prior to operation or radiation. There usually remains, however, a group of patients who are resistant to such standard nutritional supportive tech- niques. By the technique of intravenous hyperalimentation, 2500 to 4000 kcal/day can be delivered to the uncooperative patient, and the need for gastrointestinal tract assimilation can be reduced or obviated. Although the patients must usually be hospitalized to receive IVH safely and practically, the most debilitated patients in this series required only an average of 17.4 days of parenteral nutritional support to gain sufficient weight and strength to convert them to reasonable operative risks.

Wound healing and tissue tolerance for radiotherapy are related to the nutritional status of the patient. Most radical head and neck surgical procedures result in large wounds that require coverage with multiple flaps which often must be generated from a distant donor site. The magnitude of the surgical procedure which can be performed is often dictated by the probable healing capacity of the resultant wound. Since optimum nutrition usually begets optimum healing, the usefulness of intravenous hyperalimentation in the treatment of debilitated head and neck cancer patients is ob- vious. In seven of the eight patients treated with intravenous hyperalimentation prior to operation, no postoperative complications occurred, although each patient had undergone an ex- tended operation for removal of the cancer.

Malignancies of the head and neck often grow to a large size before metastasizing. These lesions may be anatomically resectable, but the resection may exceed the limits of wound healing even in the optimally nourished patient. Death occurred in this series to one patient who was treated with IVH prior to the attempted surgical removal of three separate primary lesions. The patient succumbed secondary to the complications of wound disruption and carotid artery rupture. Although weight gain, restora- tion of strength, and accelerated healing of pre- viously indolent wounds may be dramatic re- sponses to intravenous hyperalimentation, the surgeon must restrain himself from the over- zealous attack of lesions which are anatomically but not physiologically resectable.

Assimilation of food via the gastrointestinal tract is suppressed in clinically malnourished patients, and much of the administered nutrient ration can be lost in the stool. For example, the absorptive defect in severe protein- malnutrition can be corrected only after feeding

a diet containing 100 g of protein per day for at least 3 months.' Attempted enteral feeding of a blenderized diet or a chemically-defined ele- mental diet to the patients admitted to the M. D. Anderson Hospital for supportive care usually resulted in bloating, abdominal cramps, and diarrhea. However, when such patients were repleted nutritionally with IVH, they soon regained their capability to assimilate a blenderized regular diet in amounts necessary to maintain nutritional equilibrium. It is not within the scope of this discussion to speculate upon the reasons that these nutritionally repleted patients could enterally absorb food- stuffs that they were unable to absorb prior to treatment with hyperalimentation; however, protein/calorie deprivation has been shown to impair jejunal absorption rates of essential amino acids in man' and to impair the replica- tion of intestinal villus cells in animals.'

Inanition and malnutrition are two of the pre- disposing factors to bacterial and fungal sep- ticemia. Other investigators have attempted to establish a causal relationship between the administration of hyperalimentation and fungal in- fections, especially Candida albicans sepsis. They fear particularly the infectious sequelae of long- term central venous catheterization. However, with careful attention to the aseptic management of the subclavian feeding catheter and the hyperalimentation delivery tubing, catheter- related sepsis can be reduced to a reproducibly low rate. In a series of 93 patients with a wide variety of oncologic diseases recently reported from our institution,2 the incidence of catheter- related sepsis was only 2.2%. The need for rigorous aseptic management of the subclavian catheter is greatest in the patients undergoing treatment for head and neck cancer. Often these patients have pharyngocutaneous and/or tracheostomy stomas which produce secretions that can continually contaminate the catheter dressing. This dressing must be protected by a sterile plastic sheet and changed aseptically as frequently as necessary, often twice a day. Each febrile episode should be considered catheter- related, and if another source of fever cannot be identified, the catheter should be incriminated empirically and removed. Intravenous hyperalimentation can be reinstituted within 24 to 48 hours through a subclavian catheter inserted into the same or contralateral subclavian vein. In this series, a single central venous catheter was in place for as long as 91 days without complications; routine catheter replace- ment was not necessary.

No. 3 HYPERALIMENTATION IN CANCER Copeland et al. 61 I

Ideally, those patients who are to receive intravenous nutritional support should be identified prior to hospital admission. Hyper- alimentation should be utilized until weight gain has begun, and muscle strength has returned. Hyperalimentation should be discontinued during the operative period, but should be reinstituted within 1 to 3 days postoperatively. It

should be continued until the patient is able to maintain adequate nutrition via the enteral route. Using this technique, oncologic therapy can be safely recommended to a group of patients who might otherwise be denied possible curative surgical or radiation therapy because of the threat of major complications secondary to malnutrition and inanition.

REFERENCES

1. Adibi, S. A., and Allan, R. E.: Impairedjejunal absorption rates of essential amino acids induced by either dietary, caloric or protein deprivation in man. Gastroenterology 59:404-413, 1970.

2 . Copeland, E. M., MacFadyen, €3. V., Jr., McGown, C., and Dudrick, S. J.: The use of hyperalimentation in patients with potential sepsis. Surg. Gynecol. Obrfe t . 138:377-380, 1974.

3. Dey, M. G., and Ramalingaswami, V.: Reaction of the small intestine to induced protein malnutrition in Rhesus monkeys-A study of cell population kinetics in the jejunum. Gastroenterology 49: 150-157, 1965.

4. Dudrick, S. J., Wilmore, D. W., Vars, H. M., and Rhoads, J. E.: Long term total parenteral nutrition with growth, development, and positive nitrogen balance. Surgery 64:134-142, 1968.

5. Dudrick, S. J., Wilmore, D. W., Vars, H. M., and Rhoads, J. E.: Can intravenous feeding as the sole means of nutrition support growth in the child and restore weight loss in an adult? An affirmative answer. Ann. Surg. 169:974-984, 1969.

6. Tandon, B. N., Magotra, M. L., Saraya, A. K., and Ramalingaswami, V. : Small intestine in protein malnutrition. A m . J . Clin. Nufr. 21:813-819, 1968.

intravenous hyperalimentation in patients with head and neck cancer

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