Biomedical subjects
Publications and source records attributed to H J Gramm.
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The case report presents evidence for the spinal origin of the marked hypertensive responses to noxious stimuli that may occur in organ donors who fulfill the commonly accepted criteria of brain death. Cardiovascular spinal reflex activity does not invalidate these criteria. For the first time, the catecholamine plasma concentrations have been determined during spinal pressor reflex activity. Circulating epinephrine increased more markedly than norepinephrine in both cases, rising to 4.7 and 44 times the baseline concentration respectively. The relation between plasma norepinephrine and epinephrine suggests involvement of the adrenal medulla in the reflex arc. The literature on spinal hemodynamic reflexes is reviewed.
After brain death, 32 potential organ donors were studied to determine serum and plasma concentrations of hypothalamic-pituitary hormones, thyroid hormones, and cortisol over a period of up to 80 hr. Diagnosis of brain death was established either on the basis of clinical criteria (n = 16) or by angiography (n = 16). While 78% of the organ donors developed diabetes insipidus, none of the circulating hormones of the anterior pituitary gland showed a progressive decline in concentration according to their plasma half-lives. With the exception of arginine vasopressin (AVP), no hormone concentration was found to be subnormal due to the onset of brain death. The subnormal free triiodothyronine (FT3) values in 62% of cases (median FT3 of 2.2 pmol/L within the first 24 hr) and the cortisol concentration of 6.9 micrograms/dl correlate with the frequency of similar findings in patients with severe head injuries. While the adrenocorticotropic hormone (ACTH) concentrations of 10-53 pg/ml remained constant during the study period, thyroid-stimulating hormone (TSH) and human growth hormone (hGH) concentrations showed a 12- and 35-fold increase from baseline values after 30-40 hr. These results suggest that, despite the now generally accepted criteria of brain death, there is still some residual function, and thus also perfusion of the hypothalamic-pituitary neuroendocrine system. This residual function appears to be sufficient to maintain hormonal plasma levels at least in the low reference range in most donors. Hormonal depletion in organ donors subsequent to brain death, as suggested repeatedly in the literature, could not be confirmed. The analysis of serum or plasma concentration patterns of a number of hormonal parameters following brain death does not support the rationale for a routine replacement therapy of total triiodothyronine (TT3) or cortisol to maintain endocrine homeostasis prior to organ harvest. However, dexamethasone therapy may be followed by suppression of the adrenal cortex of the organ donor. In these cases, cortisol substitution may be indicated.
A patient who developed valproate-associated hepatotoxicity had significantly lower serum levels of total protein, albumin and selenium than the controls. This study shows that with the beginning of the hepatic coma metallothionein (MT) appeared in the serum mainly in the form of Zn-thionein, which altered the Zn distribution pattern of the serum in a characteristic manner. HPLC-ICP3 was successfully applied to the simultaneous speciation of elements and characterization of MT by the use of one gel permeation column.
A very severely retarded infant with a Dandy-Walker malformation was treated with valproate since the age of 6 months on account of infantile spasms. Three weeks after start of therapy dexamethasone was applied additionally because valproate was ineffective. Seventy-six days after initiation of valproate therapy the infant died with the clinical signs of fulminant valproate-associated hepatotoxicity despite the discontinuation of valproate. In combination with a febrile otitis media the child had been periodically restless and lethargic during the last week prior to liver coma. Activity of liver enzymes remained within normal limits up to two days before coma occurred. Analysis of valproate metabolites by gas chromatography/mass spectrometry yielded unusually high concentrations of the di-unsaturated metabolite E,E-2,3'-dien-valproate before and during liver failure. The concentrations of the main metabolites E-2-en-valproate und 3-keto-valproate remained within the usual range found during valproate therapy at steady state. The oxydation products 4-en-valproate and E-2,4-dien-valproate which are formed by alternative pathways and are considered to be hepatotoxic were detected in very low concentrations only. The application of carnitine, of antioxidants thought to improve the capacity of the free radical scavenger system (selen, vitamin E), and of N-acetylcysteine which can detoxify reactive drug metabolites could not prevent the fatal outcome.
A procedure for the determination of plasma catecholamine concentrations in critical care patients after dobutamine infusion is presented. A modified chromatographic system is required with an additional washing procedure to achieve maximum sensitivity and stable chromatographic conditions. The influence of storage time on the catecholamine concentrations of plasma samples is reported in detail. A time-dependent decrease in catecholamine concentrations of up to 12 and 39% was found within two and ten months, respectively.
Ether link cleavage (ELC) of T4 yielding diiodotyrosine (DIT) has recently been shown in vitro to be the major pathway of T4 metabolism in phagocytosing leukocytes. To evaluate this pathway in vivo and the possible clinical relevance of DIT measurements in diseases with increased leukocyte activity, radioimmunological studies on serum levels of DIT and other thyroid parameters were performed in 125 critically ill patients classified into 3 groups with bacterial infections according to the severity of infection and 1 group without infections. While the pattern of iodothyronine and TSH levels typical for severe nonthyroidal disorders, i.e. decreased total T3 and elevated rT3, normal or decreased total T4 and TSH, and normal free T4, was found in all four groups of intensive care patients studied, elevated serum DIT was observed only in those patients whose clinical course was complicated by severe bacterial infections. Serial measurements revealed a close temporal connection between the infection phase and increased DIT levels. Median values and 16th to 84th percentile ranges (in parentheses) of serum DIT (normal range, 0.02-0.55 nmol/L) were as follows: sepsis, 1.38 (0.32-5.14); severe nonsystemic infections such as peritonitis and abscesses, 3.84 (0.24-17.2); moderate infections such as pneumonia and tracheobronchitis, 0.44 (0.18-1.16); and critical illness without infections, 0.14 (0.08-0.30) nmol/L. These elevations of circulating DIT could neither be correlated with changes in renal function nor attributed to drug effects. The results of the present study do not allow any definitive conclusions to be made about the mechanisms underlying the phenomenon of increased serum DIT levels in infections. Apart from this open question, DIT appears to be a relatively specific serum parameter for the presence and course of severe bacterial inflammations. Its measurement could provide useful clinical information, particularly for monitoring the time course of deep-seated infections.
One of the main problems faced by transplantation medicine is the lack of suitable donor organs. The success of organ transplantation depends on the quality of the organ to be transplanted. The initial function of the transplant depends on the quality of preparation. The aim of efforts after brain death is to maintain the morphological and functional integrity of the donor organ in situ. At our clinic, all potential organ donors undergo direct arterial pressure measurement and many receive a Swan-Ganz catheter. Catecholamine administration--varied on the basis of the hemodynamic parameters--is not associated with an impairment of organ function. Electrolyte determinations at 2-hour intervals and close laboratory controls are obligatory. These intensive-care measures are necessary because of the occurrence of severe metabolic and hemodynamic imbalances. A partly transient diabetes insipidus is the most frequent homeostatic disorder. In addition, severe electrolyte imbalances, disturbed glucose utilization and hypotension may be observed. Our investigations on the plasma concentration course of thyroid hormones, ACTH and cortisol after the onset of brain death suggest that the secretion of pituitary hormones is maintained until total necrosis of the pituitary gland occurs 30 to 40 hours later. The detection of circulating ADH up to 24 hours after the onset of brain death, despite the angiographically confirmed cessation of cerebral circulation, suggests that there may be a residual perfusion of hypothalamus and pituitary. The blood levels of epinephrine, norepinephrine and dopamine measured in brain-dead patients not receiving catecholamines were in part considerably above the reference level. Our data suggest that vigorous intensive care management increases the number and quality of organs suitable for transplantation and reduces to a minimum the incidence of premature organ losses.
In septic patients the clinical course of the disease is characterized by high DIT and rT3 serum concentrations as well as a low T3-syndrome. While rT3 is elevated in almost all critically ill patients, the increase in DIT is indicative of severe infection. Prolactin levels are regularly elevated in sepsis although to variable degrees. Catecholamines and vasopressin should be regarded as acute responders. The pattern of cortisol secretion is uncertain. In most situations the secretion appears to be elevated; the circadian rhythm is disturbed.
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Explore the source record for details and available documents.
Acute renal failure (ARF) in newborns and infants is a serious postoperative complication. Peritoneal dialysis is considered the treatment of choice, but is often impossible postoperatively. In adult patients or older children, continuous arteriovenous hemofiltration (CAVH) has been established for 10 years. In 1985, Ronco published case reports on four newborn infants treated with CAVH using a specially designed hemofilter. In between, a few more case reports have been published. We report a case of postoperative septic ARF in an 8-week-old girl with a body weight of 4000 g. We used the Minifilter (Amicon Corp.) connected to a femoral arterial Shaldon catheter and initially a central venous line, later a subclavian Shaldon catheter. Intermittent hemodialysis without ultrafiltration was performed as well. With ultrafiltration rates of 2 to 24 ml/h, mean 12.8 ml/h, we achieved an impressive loss of weight and the pulmonary function improved. The baby died on the 5th day of CAVH treatment of septic multiorgan failure. Even though the small patient did not survive, we demonstrated the feasibility of the method in newborns. CAVH is recommended for overhydrated babies with oligoanuric ARF, but it is not sufficient as a substitute for dialysis in these patients.
Parenteral nutrition via an indwelling central venous catheter was undertaken at home over a total period of 24,747 days in 34 patients with the short-bowel syndrome (of various causes). In some of the patients there developed complete adaptation of the residual intestine so that parenteral nutrition could be terminated. Complications were: infection, thrombosis, pulmonary embolism and metabolic problems. But the method proved to be suitable for improving the quality of life of these patients.
The effect of pentobarbital treatment in a mean dose of 30 mg/kg/day on the clearance of hexobarbital (Evipan) and dipyrone (Novalgin) has been evaluated in critical care patients receiving a large number of drugs as comedication. Eleven patients treated with pentobarbital showed a hexobarbital half-life of 2.79 h and a total plasma clearance of 9.80 ml X min-1 X kg-1 as compared to 10 patients without pentobarbital administration in whom there was a significantly longer half life (6.92 h) and lower clearance (2.97 ml X min-1 X kg-1). The kinetics of hexobarbital were correlated with the urinary excretion of D-glucaric acid, a non-invasive parameter of drug metabolising activity. In 10 patients on pentobarbital, the total plasma clearance of N-4-methyl-aminoantipyrine, the active form of dipyrone, did not differ from that in 8 patients not receiving pentobarbital. As drug kinetics show great variability in these patients, it is difficult to discriminate enzyme induction from other mechanisms, for example competitive inhibition or changes in volume of distribution. In the presence of pentobarbital, however, induction of drug metabolising enzymes should be considered as a possible reason for the higher clearance of hexobarbital.
Intravenous solutions contain both essential and nonessential trace elements. The manufacturer is not obliged to declare the concentration of trace elements contained therein. Therefore, a study was done to investigate the concentration of magnesium, copper, chromium, manganese and cobalt, as well as a possible contamination by aluminum and nickel, in 15 solutions used for parenteral nutrition and blood products applied in Germany. Measured against the daily parenteral requirements, negligible concentrations were found for all essential trace elements with the exception of chromium and cobalt. A marked contamination by the nonessential metal ions aluminum and nickel was detected in the 5% protein- and 20% albumin-solutions. Aluminum concentration was 16-49 mumol/l in the blood products and up to 4.9 mumol/l in the nutrient solutions. The concentration of nickel found in the protein- and hydroxyethyl starch solutions was 250 times higher than the normal serum level. It must be assumed that different manufacturing procedures lead to the different degrees of contamination of the solutions (up to 100%). In view of more recent publications, the aluminum contamination may be a potential hazard to patients with prolonged parenteral nutrition and certain risk groups among the critically ill.
The intracranial pressure (ICP) response to the lumbar extradural injection of bupivacaine hydrochloride was measured in two patients on a total of 29 occasions. In the first patient, mean ICP increased from an average figure of 18.8 mm Hg to 39.5 mm Hg after the injection of 10 ml of solution. This increase was maintained for an average of 4.5 min. Both the magnitude and the duration of the increase were less when 5 ml was injected. The second patient had a normal baseline ICP, but the injection of bupivacaine 10 ml produced an increase from a mean of 9.3 mm Hg to 15.6 mm Hg. Injection of the same volumes of physiological saline in the second patient induced increases in ICP similar to those obtained with bupivacaine. There was a good correlation between baseline ICP and the increase produced by the extradural injection. It is concluded that extradural anaesthesia must be used with extreme caution in patients with reduced intracranial compliance, and should not be used at all in a patient with intracranial hypertension or a space-occupying lesion.
Blood gas analysis devices routinely used in clinical practice measure pH, pCO2 and pO2 directly, while all other values they specify are calculated on the basis of nomograms. In the presence of higher concentrations of biologically useless forms of haemoglobin, calculation of the haemoglobin saturation (% O2 Hb) leads to a clinically relevant false assessment of oxygen availability. A case is described in which toxic methemoglobinaemia occurred postoperatively after resumption of long-term medication with 150 mg 4,4-diaminodiphenylsulfone (DADPS). Increasing methaemoglobin values up to maximal 17.7% at a total haemoglobin of 11.3 g/dl correlated with the symptoms of cyanosis and respiratory distress. This symptom complex, which is not atypical postoperatively, could not be clarified by differential diagnosis with the aid of cardiac output measurements and arterial blood gas analyses. The cardiac index amounted to 4.1 l/m2 at a pulmonary capillary wedge pressure of 8 mmHg; the arterial partial oxygen pressure was between 16 and 19 kPa. Only the differential determination of oxihaemoglobin, CO-haemoglobin and methaemoglobin with an oximeter yielded evidence of severe arterial hypoxaemia and made therapy possible.