Acute hepatic and renal insufficiency is correctly considered a most serious complication of the postoperative period, and especially of the postreanimation period. The gross disturbances of metabolic processes and severe intoxication developing in these cases lead to the development of a comatose state and frequently to a fatal outcome.
Hypoxia of various origins underlies hepatic and renal insufficiency, but, as mentioned above in the experimental part, these complications are most often the result of prolonged hypotension, and disturbance of regional and microcirculation. The development of anaemia or acute respiratory insufficiency on such an unfavourable background aggravates the damage to the liver and kidneys.
In the postreanimation period of patients who have suffered severe trauma or massive loss of blood, the renal insufficiency develops more frequently than hepatic. In addition to the causes mentioned above, it can also be provoked by haemolysis of various aetiology, the crush syndrome, and certain other factors. Neverov divides cases of renal insufficiency into three types:
(1) compensated disturbance of renal function; (2) a subcompensated form of renal insufficiency; (3a) a decompensated form with incomplete renal block; (3b) full renal block.
The findings of the authors cited indicate that, with severe traumatic shock, the compensated form of renal insufficiency is that which develops most frequently, and calls for no special therapy. Decompensated renal insufficiency with incomplete renal block develops in 5 per cent of cases and full renal block in 3 per cent. Whereas, with incomplete block the administration of osmotic diuretic remedies has a positive effect on the course of the pathological process, with full renal block it becomes necessary to apply extracorporeal haemodialysis. According to Sternin, a fatal outcome in cases of renal insufficiency is mainly due to three causes: hypertension, hypervolaemia, which leads to oedema of the lungs and brain, and disturbance of vitally important centres as a result of metabolic acidosis.
In the Hospital clinical reanimation department patients who have experienced clinical death without having previous serious disturbances of haemodynamics the impairment of renal function in the early restorative period was usually mild and showed as urinary syndromes and a small rise in the blood’s residual nitrogen content. Such disturbances call for conservative therapy aimed mainly at preserving and correcting water-electrolyte balance. The restoration of renal function is stable. In the selective follow-up of 28 patients who had survived clinical death due to various causes, impairment of renal functioning was not found after one to three years. Severe damage to these organs after clinical death is unique.
Marked impairment of renal function, up to the development of oliguria and anuria, was observed, as was to be expected, in patients who had suffered protracted hypotension as a result of massive loss of blood or multiple trauma.
A main cause of the development of renal insufficiency in cases of massive blood loss and multiple trauma is the disruption of renal blood flow through centralization of circulation. When arterial pressure drops below 60-70 mm Hg, as we know, the excretory function of the kidneys is sharply reduced and may even cease. The experimental research of Vashetina et al. showed that, as early as the initial, torpid stage of shock, renal blood flow dropped to 40 per cent of its initial amount. Moreover, when the loss of blood is not compensated, and the volume of circulating blood is reduced impairment of the kidney’s urine excretory function may be due to an increase in the reabsorption of water in the renal tubules as a result of the heightening of plasma osmotic pressure and the secretion of the antidiuretic hormone.
In this connection we attach great significance to rapid replacement of the volume of circulating blood, regulation of water-salt and acid-base equilibrium in the prophylaxis of renal insufficiency in the early stages of treating traumatic shock and terminal states. Intravenous transfusion of gangliolytic remedies and of mannitol, rheopolyglucine and euphyllin are very effective measures to improve renal blood flow. Osmotic diuretic remedies are administered so as to avoid hyperhydraemia. Berkutov’s school uses the same therapeutic tactics.
With anuria and oliguria and no effect from conservative therapy, in conditions of azotaemia, hyperkaliaemia, and other disorders of water-electrolyte balance, extracorporeal haemodialysis is employed. With combined renal and respiratory insufficiency, haemodialysis is employed in the reanimation department in combination with artificial ventilation of the lungs. When the patient can be moved, he is transferred to the nephrology department after the necessary reanimation measures have been taken.
Haemodialysis, it must be noted, is most complicated in patients suffering from acute renal insufficiency combined with severe disorders of haemodynamics. Haemodialysis then occasionally becomes intolerable or ineffective because of a sharp drop in arterial pressure, the need to carry out the haemodialysis at a low volumetric rate of blood flow through the artificial kidney, and frequent discontinuations of the process in order to treat disturbances of haemodynamics. In the opinion of the authors cited, the prognosis of the last two categories of patients depends in the main on other factors and not on the course of the severe renal insufficiency.
The isolated reports in the literature of simultaneous application of extracorporeal circulation and haemodialysis give grounds to accept the desirability of employing these measures in cases of severe renal insufficiency developing in conditions of marked disturbance of haemodynamics.
The development of oliguria and anuria is sometimes preceded by disturbance of hepatic function. According to Bromage and Schneider, liver cells are extraordinarily sensitive to hypoxia, and it is only because of their colossal regenerative capacity that the organism is able to cope with its effects. When hepatic insufficiency arises in conditions of hypoxia, persistent disturbances of haemodynamics occur and that in turn, as mentioned above, leads to the development of oliguria and anuria. Secretion of the iron-containing protein ferritin, which catalyses the oxidation of adrenalin into adrenochrome, from liver cells is a main cause of the development of persistent hypotonia. The pathogenesis of the acute hepatic insufficiency that develops as a result of terminal states has not, as yet, been sufficiently studied.
Impairment of urea synthesis in the liver and the development of hyperammonaemia and the accumulation of ammonia in the brain are apparently of some importance in the development of severe lesions of the vital organs. The disruption of the Krebs cycle that occurs then is accompanied with a drop in oxygen tension in the central nervous system and the development of coma. There are also indications that the accumulation in the blood of certain amino acids, as a result of disturbance of deamination in the liver, depresses oxidative processes.
Treatment of the hepato-renal insufficiency syndrome is extremely complicated and so far of low efficiency, especially when hepatic insufficiency predominates. According to Topchiashvili, it is necessary above all, in the early stages of the development of hepato-renal insufficiency to raise arterial pressure by means of intravenous transfusion of polyglucine and hormone drugs. Sodium bicarbonate is administered in order to overcome metabolic acidosis, and glucose and insulin to restore the liver’s energy resources.
In the opinion of Topchiashvili, injection of glucose into the umbilical vein after it had been bared, bougienaged and cannulated is highly effective; but when sodium ions are retained in the tissues it is not completely safe to introduce hypertonic solutions as it can lead to oedema of the brain and lungs. When renal insufficiency predominates over hepatic, then the administration of osmotic diuretic media is also indicated during the first two days of the development of renal-hepatic insufficiency syndrome. When such therapy has no positive effect, then extracorporeal haemodialysis is employed. As a rule, after haemodialysis, blood levels of urea, residual nitrogen, and potassium ions decrease.
It is quite clear that treatment of hepato-renal insufficiency should be commenced as soon as possible; but it is extremely difficult to diagnose hepatic insufficiency in its early stages as the clinical symptoms are very limited. The most reliable first signs are a drop in blood prothrombin level and suppression of the liver’s secretory functions. An increase in activity of certain enzymes in the blood can also be a valuable diagnostic sign, in particular that of glutamate-oxalate transaminase and especially of glutamate-pyruvate transaminase.
There is reason to hope that study of hepatic blood flow will allow the development of hepatic insufficiency to be foreseen and, consequently, prophylactic measures to be taken in time. The rheographic method of determining hepatic blood flow, however, is very complicated. This research is being carried out at present in Hungary in Kovacz’s laboratory. The prophylaxis of hepatic insufficiency, like that of renal insufficiency, is mainly a matter of avoiding or eliminating hypoxia. With the development of hepatic insufficiency pathogenic therapy directed to correcting metabolic disorders is widely employed in combination with measures aimed at eliminating hypoxia.
Tholen and Colombi recommend introducing a group of enzymes aimed at accelerating synthesis of energy-producing phosphates. For that purpose they used coenzyme A, nicotinamide, adenine dinucleotide, cocarboxylase. The proposal to treat acute hepatic insufficiency by injecting 1-glutamine also presents interest. Underlying this method is the idea of correcting phenylalanine metabolism. With acute hepatic insufficiency phenylalanine is not hydroxylated, which leads to the formation of toxic phenyl pyruvate and phenyl acetate. Administration of 1-glutamine provides the transition of phenyl pyruvate into phenylacetyl glutamine. L-glutamine also promotes detoxication and synthesis of nucleic acids and proteins.
Perfusion of the liver with oxygenated blood is now being taken into clinical practice. Its use in particular to treat acute hepatic insufficiency in children and to prevent this complication during certain surgical operations has been reported by Manevich et at., who utilized the recanalized umbilical vein to introduce blood. Good results were obtained in three out of six cases of hepatic insufficiency, and the development of the complication was avoided in all 16 children operated on for portal hypertension.
Attempts to treat acute hepatic insufficiency by means of cross circulation, in order to compensate the functional insufficiency of the recipient’s liver by the donor’s healthy one, are of undoubted interest. Traege et al. reported the use of cross circulation to treat a young girl dying of acute hepatic coma as a result of viral hepatitis. The patient’s mother was the donor. Three seances lasting 12, 10, and 8.5 hours were carried out. The patient recovered, and no serious complications whatsoever were encountered in the donor. Muller et al. described a similar case of the use of cross circulation to treat a 26-year-old man in a state of hepatic coma. The donor was an elderly man of 76 who had been brought out of clinical death with only his somatic functions restored and the cerebral cortex not functioning. Recovery of the recipient was obtained in this case as well.
Earlier experimental research in the transplanting of homologous and heterologous livers has now enabled this method to be employed in the clinic.
Successful treatment of hepatic coma by means of connecting the patient’s vessels to a pig’s liver by a group of investigators at the Medical Academy was reported by M. O. Sternin to a visiting session of our Laboratory.
Blood substitution operations, it should be noted, are now acquiring great importance. Glozman reported successful employment of this operation on a patient with hepatic insufficiency. With patients who have experienced clinical death, however, blood substitution as a means of detoxication is best carried out in the earlier stages.
Blood substitution in the early restorative period, with elimination of metabolic disturbances, serves to normalize the electrolyte balance of the blood.
The overcoming of anaemia prevents the development of hepatorenal insufficiency and so creates optimum conditions for a favourable course in the subsequent restorative period.
From the experimental findings it can be said that the best effect both as regards avoiding acute hepato-renal insufficiency, and as regards the outcome of treatment, is obtained when the substitution is made during the first hours after resuscitation. As the time elapsed from the moment cardiac activity and respiration are restored lengthens, the effectiveness of blood substitution falls.
There are now not a few clinical reports of successful withdrawal of patients from clinical death as a result of this operation applied in the first few hours after the restoration of cardiac activity. We recently received a report of an interesting case from a Reanimation Centre. A 28-year-old worker received an electric shock; by the moment the reanimation team arrived he had been ten minutes in a state of clinical death. The measures applied on the spot enabled weak cardiac activity and respiration to be restored. The patient arrived at the Reanimation Centre unconscious and in a grave condition. After substitution of blood his condition improved. Two weeks later he was discharged in good condition.
The clinical findings also give grounds for believing that partial substitution of blood when done in the first 12 hours after poisoning by haemolytic poisons or acute renal insufficiency as a result of postabortion sepsis, and in haemolytic jaundice of the newborn, can be a very effective method of detoxication and correction of metabolic processes.
One of the most common after-effects of blood substitution in patients after a terminal state provoked by blood loss is the phenomenon of ‘post-transfusional anaemia’. To eliminate or avoid the massive transfusion syndrome it has been found necessary to resort to repeated transfusion of fresh blood of the same group and of packed red cells. Cases have been reported, moreover, in which the transfusion of large quantities of blood conserved with citrate solution caused metabolic acidosis in the newborn with haemolytic jaundice. This can be avoided by slow intravenous injection of a solution of sodium bicarbonate.
In our opinion preference should be given to heparinized blood over citrated when substituting blood. Massive introduction of heparinized blood does not lead to the development of hyperkaliaemia, hypocalcaemia and hypomagnaemia, does not cause acidosis, and does not involve any danger of citrate intoxication, especially in patients with disturbances of liver function.
All the methods of clinical treatment of hepatic insufficiency described above are still in the stage of development and further improvement. Nonetheless there is every reason to believe that they will be widely applied in the near future to treat this grave complication that develops in the postoperative or postreanimation period.