[Legal considerations in the care of patients with "terminal dehydration" in Germany]. / Rechtliche Rahmenbedingungen in der Versorgung von Patienten mit "terminaler Dehydration" in Deutschland.

BACKGROUND: The legal framework for fluid management in the palliative care setting varies between continents and even between countries. OBJECTIVES: What legal implications must be taken into account in Germany in dealing with "terminal" dehydration? MATERIALS AND METHODS: Relevant publications in English and German have been identified. Notably, German recommendations and guidelines were reviewed, whereas national mindsets were contrasted with those of other countries like the United Kingdom and Canada. RESULTS: Our legal considerations are in line with the recommendations of the German Federal Medical Association. Key components are "patient autonomy", "best possible symptom control" and a "steady therapeutic risk-benefit assessment". Dehydration should then continue to be regarded as a "symptom" that must be "controlled" as long as it can be improved by therapeutic means and as long as the patient is not opposed to this approach. However, if dehydration remains therapeutically refractory, it is justified either not to initiate clinically assisted hydration (CAH) or to stop the ongoing therapy. The "shared decision-making model" practiced in Canada is diametrically opposed to this approach, where paternalistic decision-making is possible, provided that patients or relatives appear to be ill-informed and unprepared to decide "correct" according to expert opinion. CONCLUSIONS: A "non-refractory" state of dehydration at the end of life must not be left untreated under German law and must not be used as an option to hasten the death process if the development of dehydration does not correspond to the patient's will or if this will cannot be determined.

[Ethical implications in the therapeutic management of dehydrated patients at the end of life]. / Ethische Implikationen bei der Therapie von dehydrierten Patienten am Lebensende.

BACKGROUND: The ethical framework for fluid management in the palliative care setting can vary. OBJECTIVES: What are the relevant ethical implications related to dehydration during end-of-life care and what are the special requirements we need to consider as far as "terminal dehydration" is concerned? MATERIALS AND METHODS: A comprehensive literature search was conducted to identify relevant articles published in English and German. RESULTS: Our inferences represent an attitude rather than an evidence-based position-a fact that is due to the underlying normative and ethical references which are hardly amenable to statistical evaluation. As far as ethical considerations are concerned, evidence is lacking to support clear decision-making and, thus, does not justify moving away from established concepts of clinically assisted hydration (CAH) at the end of life as long as measures can be effectually implemented. CONCLUSIONS: Dehydration must not be considered a measure to hasten death. Hence, dehydration in the palliative care setting must be regarded a "symptom" that should be "controlled" if it can be corrected by therapeutic means and if the patient's will does not contradict that approach. However, if CAH is futile, it is justified to refuse or stop it.

["Terminal" dehydration : Differential diagnosis and body of evidence]. / "Terminale" Dehydratation : Differenzialdiagnose und Evidenzlage.

Dehydration in palliative care patients can be associated with increased morbidity and mortality and is nevertheless therapeutically controversial. This article provides an overview of possible causes of dehydration at the end of life and places special emphasis on "terminal" dehydration in the dying. Empirical attitudes of healthcare professionals and persons concerned (patients and relatives) as well as evidence-based findings on "terminal" dehydration are elucidated and the limitations are described. Finally, it is concluded that the appropriate detection of the mode of dehydration (including its underlying pathophysiology) as well as the clinical evaluation of the "reversibility" of the symptoms after fluid therapy, is of central importance in establishing the indications for clinically assisted hydration (CAH).

How to manage terminal dehydration.

Although dehydration is a serious condition associated with significant morbidity and mortality in palliative care patients, as in any other patient group, treatment remains controversial. A narrative review of the causes of dehydration during end of life was conducted paying special attention to the nature of terminal dehydration. A comprehensive search of the literature was performed to identify relevant articles published in English and German languages between 1960 and 2018. Currently available options for bed-side evaluation and therapeutic approaches were critically appraised and areas of future research are emphasized. The following inferences can be derived: 1) the available evidence does not support a clear decision in favor or against fluid therapy during the dying phase. 2) There is inadequate precision of the term end of life care (ELC) and insufficient differentiation between modes of dehydration of palliative care patients. 3) Evaluation of dehydration based on its clinical appearance is considered the method of choice compared to invasive procedures. 4) Detailed clinical assessment of symptom reversibility in terminal dehydration by an appropriate fluid challenge is mandatory in the decision-making process. 5) If despite adequate rehydration measures, complete reversibility of the clinical picture of dehydration can no longer be achieved since organ systems are gradually deteriorating, the cessation of clinically assisted hydration (CAH) can be considered. 6) If symptoms of dehydration are reversible after fluid challenge and no other patient wishes to the contrary are known, fluid management should be continued in the context of symptom control. 7) Hyperhydration represents a considerable threat during fluid management that needs to be prevented by noninvasive monitoring procedures. In conclusion, if CAH is applied as a part of ELC the hydration status needs to be individually appraised and all therapeutic measures constantly need to be adapted to the findings of diligent monitoring procedures.

["Terminal" dehydration, part 2 : Medical indications and therapeutic approach]. / "Terminale" Dehydratation, Teil 2 : Medizinische Indikationsstellung und therapeutisches Vorgehen.

The approach in the clinical fluid management of the dying is still controversially discussed in specialist circles and also in the general population. In this article the importance of establishing the therapeutic indications is emphasized against the background of a lack of evidence. Options to achieve noninvasive objectification of assumed dehydration as well as assessment of the reversibility of the symptoms are shown and the importance of monitoring of all therapeutic actions is discussed. The pathophysiological foundation of reversible disorders of fluid homoeostasis are described and distinguished from the irreversible disorders leading to terminal dehydration. If clinically assisted hydration (CAH) is indicated, the hydration status must be assessed individually as well as in advance and all therapeutic measures must be constantly adjusted to the results of non-invasive monitoring procedures.

["Terminal" dehydration, part 1 : Differential diagnosis and body of evidence]. / "Terminale" Dehydratation, Teil 1 : Differenzialdiagnose und Evidenzlage.

Dehydration in palliative care patients can be associated with increased morbidity and mortality and is nevertheless therapeutically controversial. This article provides an overview of possible causes of dehydration at the end of life and places special emphasis on "terminal" dehydration in the dying. Empirical attitudes of healthcare professionals and persons concerned (patients and relatives) as well as evidence-based findings on "terminal" dehydration are elucidated and the limitations are described. Finally, it is concluded that the appropriate detection of the mode of dehydration (including its underlying pathophysiology) as well as the clinical evaluation of the "reversibility" of the symptoms after fluid therapy, is of central importance in establishing the indications for clinically assisted hydration (CAH).

Glutamine and alanyl-glutamine dipeptide reduce mesenteric plasma extravasation, leukocyte adhesion and tumor necrosis factor-α (TNF-α) release during experimental endotoxemia.

Glutamine (GLN) appears to be an essential nutrient during organism development and critical illness. The aim of our study was to evaluate the effects of GLN and its generic preparation alanyl-glutamine-dipeptide (DIP) on the microcirculation in endotoxemia in rats and its effects on tonus or aortal rings in vitro. Male Lewis rats (n=40) were separated in 4 groups. Group 1 (CON) served as healthy control group while the other groups received an endotoxin bolus i.v. (5 mg/kg lipopolysaccharide, LPS i.v.). In group 3 (LPS+GLN) 0.75 g/kg-1 GLN i.v. before LPS challenge was administered. In group 4 (LPS+DIP) DIP containing 0.75 g/kg GLN was given. Leukocyte-endothelial interactions and mesenteric plasma extravasation were determined at 0, 1 and 2 hours during the experiment by intravital fluorescence microscopy (IVM). Cytokine release (TNF-alpha, IL-1 beta, IL-6, IL-10) was measured by ELISA. GLN treatment reduced leukocyte adherence (-49.7% vs. LPS group, p<0.05) and plasma extravasation (-12.3% vs. LPS group, p<0.05) significantly during endotoxemia compared to untreated LPS animals. In group 4 (DIP+LPS), a decrease of leukocyte adherence (-56.0%) and mesenteric plasma extravasation (-18.8% vs. LPS group, p<0.05) was also found. TNF-alpha levels were reduced in both GLN and DIP (p<0.05). In vitro experiments demonstrated that glutamine agents could attenuate the response to contracting agents in presence of the vascular endothelium, implying nitric oxide pathway. In vivo, GLN as well as DIP pre-treatment diminish the detrimental impact of endotoxemia on the mesenteric microcirculation and the TNF-alpha release, the effects whose clinical importance should be further examined.

[Nutrition of critically ill patients in intensive care]. / Ernährung kritisch Kranker auf der Intensivstation.

A concept for combined enteral and parenteral nutrition for critically ill patients is described in which endogenous substrate production during the acute phase of illness is taken into consideration and hyperalimentation is avoided. The nutritional goal is defined by multiplication of the base rate, i.e. body weight (BW) in kg as delivery rate in ml/h (wedge 24 kcal/kg BW/24 h), with a target factor, which varies between 0.2 and 1.8. An equivalent composition of enteral and parenteral nutrition allows a transition between both forms without problems. Simultaneously, immunologic aspects of nutrition are considered as well and both forms of nutrition are complemented by immune-modulating substrates such as glutamine and antioxidants.

[Nutritional concepts for patients under intensive care]. / Ernährungskonzepte bei Intensivpatienten.

The clinical outcome of critical ill patients can be improved by standardised nutrition. However, trials meeting the standard of evidence-based medicine are rare. For this reason, standards still have to be based on pathophysiological considerations. We describe a concept of combined nutrition for critically ill patients which avoids hyperalimentation and considers also immunological aspects. An equivalent composition of enteral and parenteral nutrition allows a transition between both forms without problems. The nutritional goal is defined by multiplication of the base rate, i. e., body weight in kg as delivery rate in mL/h, - corresponding to 24 kcal/kg BW/24 h - with a target factor which varies between 0.2 and 1.8. Both forms of nutrition are complemented by immune-modulating substrates as glutamine and antioxidants.

Structure and organisation of 47 nutrition support teams in Germany: a prospective investigation in 2000 German hospitals in 1999.

OBJECTIVE: Evaluation. Contrary to the Anglo-American region, very little is known in Germany on the structure and organisation of nutrition support teams (NST). DESIGN: Prospective investigation of the structure and organisation of German NST, using standardised interview questionnaires. SETTINGS: Hospitals with more than 250 beds in Germany. SUBJECTS: German NST (n=47). INTERVENTIONS: Face-to-face interview in 1999, using a standardised questionnaire. RESULTS: From a total of 2000 German hospitals, NST have been established at 47 hospitals (2.3%). Most NST are affiliated to a large university hospital or an academic teaching hospital. In general, the NST are not independently operating units but are affiliated to a special discipline, and were in operation for an average of 8 y. The NST cared for a median of 65 outpatients annually. At the university hospitals in average, 477 in-patients were treated per year, at the teaching hospitals 400 and at all other hospitals 179. The work of the NST centred on enteral nutrition. A total of 47% of the physicians, 19% of the nurses and 19% of the dietitians in the NST held a nutrition-specific additional qualification. A total of 2% of the physicians, 68% of the nurses and 77% of the dietitians are exclusively responsible for the NST. More than 70% of the financing of the personnel was secured through third-party funds. CONCLUSION: In Germany, neither uniform nor comprehensive patient care by NST existed in 1999. More than 50% of all NST members do not hold a nutrition-specific additional qualification. Frequently, besides their tasks in the team, the NST staff also carries out other clinical functions. Contrary to the American NST, the German NST are not interdisciplinary operating units but are primarily financed through third-party funds of the industry.

Immune-modulatory actions of arginine in the critically ill.

Current trials of immune-enhancing diets suggest several beneficial clinical effects. These products are associated with a reduction in infectious risk, ventilator days, ICU and hospital stay. However, methodological weaknesses limit the inferences we can make from these studies. Furthermore, improvements in outcomes were largely seen in surgical patients and in patients who tolerated critical amounts of formula. We propose that the beneficial findings cannot easily be extrapolated to other patient populations since there is suggestion from clinical trials that the sickest patients, especially those with severest appearances of sepsis, shock and organ failure may not benefit or may even be harmed. In these conditions we hypothesize that systemic inflammation might be undesirably intensified by immune-enhancing nutrients like arginine in critically ill patients. In this paper, we review the purported effects of arginine on the immune system and organ function to understand the scientific rationale for its inclusion into enteral feeding products. We conclude that patients with the most severe appearances of the systemic inflammatory response syndrome should not receive immune-enhancing substrates which may aggravate systemic inflammation and worsen clinical outcomes.

Impact of sepsis, lung injury, and the role of lipid infusion on circulating prostacyclin and thromboxane A(2).

OBJECTIVE: To investigate whether plasma levels of prostacyclin (PGI2) and thromboxane A(2) (TxA2) are a function of the infusion rate of soybean-based fat emulsions, severity of systemic inflammation, and pulmonary organ failure. DESIGN: Prospective, randomized, crossover study. SETTING: Intensive care unit of a university hospital. PATIENTS: Eighteen critically ill patients, ten presenting with severe sepsis, eight with SIRS or sepsis complicated with ARDS. INTERVENTIONS: Patients were randomly assigned to receive rapid fat infusion over 6 h (rFI) or slow fat infusion over 24 h (sFI) along with parenteral nutrition. MEASUREMENTS AND RESULTS: The stable prostanoids 6-keto-PGF1alpha and TxB2 were measured in arterial and mixed venous blood samples, and at 6-h periods trans-pulmonary balances (TPB) were calculated. Free linoleic acid fraction was determined in arterial blood. rFI induced greater increase of linoleic acid than sFI in both groups. Enhanced prostanoid levels and correlations with linoleic acid availabilities were found, however, in ARDS patients only, revealing the highest sepsis- and lung injury scores. Averaged TPB per 24 h was positive in the sepsis group and negative in the ARDS group as rFI induced lowest TPB values for TxB2 at 6 h. CONCLUSION: The quantity of prostanoids formed and their subsequent utilization are dependent on the availability of precursor linoleic acid and are probably affected by the severity of SIRS or sepsis and the existence of pulmonary organ failure, respectively. Because TxA2 might be extracted by the injured lung, rapid infusion of soybean-based fat emulsions should be avoided in patients suffering from severe pulmonary organ failure.

Effects of intravenous fat emulsions on lung function in patients with acute respiratory distress syndrome or sepsis.

OBJECTIVE: To investigate whether rapid or slowly infused intravenous fat emulsions affect the ratio of prostaglandin I2/thromboxane A2 in arterial blood, pulmonary hemodynamics, and gas exchange. DESIGN: Prospective, controlled, randomized, crossover study. SETTING: Operative intensive care unit of a university hospital. PATIENTS: Eighteen critically ill patients. Ten patients were stratified with severe sepsis, and eight patients had acute respiratory distress syndrome (ARDS). INTERVENTIONS: Patients were assigned randomly to receive intravenous fat emulsions (0.4 x resting energy expenditure) over 6 hrs (rapid fat infusion) or 24 hrs (slow fat infusion) along with a routine parenteral nutrition regimen, by using a crossover study design. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary hemodynamics as well as gas exchange measurements were recorded via respective indwelling catheters. Arterial thromboxane B2 and 6-keto-prostaglandin-F1alpha plasma concentrations were obtained by radioimmunoassay, and 6-keto-prostaglandin-F1alpha/thromboxane B2 ratios (P/T ratios) were calculated. Data were collected immediately before and 6, 12, 18, and 24 hrs after onset of fat infusion. In the ARDS group, P/T ratio increased by rapid fat infusion. Concomitantly, pulmonary shunt fraction, alveolar-arterial oxygen tension difference [P(a-a)o2]/Pao2, and cardiac index increased as well, whereas pulmonary vascular resistance and Pao2/Fio2 declined. After slow fat infusion, a decreased P/T ratio was revealed. This was accompanied by decreased pulmonary shunt fraction, lowered P(a-a)o2/Pao2, and increased Pao2/Fio2. Correlations between plasma concentrations of 6-keto-prostaglandin-F1alpha or thromboxane B2 and measures of respiratory performance could be shown during rapid and slow fat infusion, respectively. In the sepsis group, the P/T ratio remained unchanged at either infusion rate, but pulmonary shunt fraction and P(a-a)o2/Pao2 decreased after rapid fat infusion, whereas Pao2/Fio2 increased. CONCLUSION: Pulmonary hemodynamics and gas exchange are related to changes of arterial prostanoid levels in ARDS patients, depending on the rate of fat infusion. In ARDS but not in sepsis patients clear of pulmonary organ failure, a changing balance of prostaglandin I2 and thromboxane A2 may modulate gas exchange, presumably via interference with hypoxic pulmonary vasoconstriction.

Should immunonutrition become routine in critically ill patients? A systematic review of the evidence.

CONTEXT: Several nutrients have been shown to influence immunologic and inflammatory responses in humans. Whether these effects translate into an improvement in clinical outcomes in critically ill patients remains unclear. OBJECTIVE: To examine the relationship between enteral nutrition supplemented with immune-enhancing nutrients and infectious complications and mortality rates in critically ill patients. DATA SOURCES: The databases of MEDLINE, EMBASE, Biosis, and CINAHL were searched for articles published from 1990 to 2000. Additional data sources included the Cochrane Controlled Trials Register from 1990 to 2000, personal files, abstract proceedings, and relevant reference lists of articles identified by database review. STUDY SELECTION: A total of 326 titles, abstracts, and articles were reviewed. Primary studies were included if they were randomized trials of critically ill or surgical patients that evaluated the effect of enteral nutrition supplemented with some combination of arginine, glutamine, nucleotides, and omega-3 fatty acids on infectious complication and mortality rates compared with standard enteral nutrition, and included clinically important outcomes, such as mortality. DATA EXTRACTION: Methodological quality of individual studies was scored and necessary data were abstracted in duplicate and independently. DATA SYNTHESIS: Twenty-two randomized trials with a total of 2419 patients compared the use of immunonutrition with standard enteral nutrition in surgical and critically ill patients. With respect to mortality, immunonutrition was associated with a pooled risk ratio (RR) of 1.10 (95% confidence interval [CI], 0.93-1.31). Immunonutrition was associated with lower infectious complications (RR, 0.66; 95% CI, 0.54-0.80). Since there was significant heterogeneity across studies, we examined several a priori subgroup analyses. We found that studies using commercial formulas with high arginine content were associated with a significant reduction in infectious complications and a trend toward a lower mortality rate compared with other immune-enhancing diets. Studies of surgical patients were associated with a significant reduction in infectious complication rates compared with studies of critically ill patients. In studies of critically ill patients, studies with a high-quality score were associated with increased mortality and a significant reduction in infectious complication rates compared with studies with a low-quality score. CONCLUSION: Immunonutrition may decrease infectious complication rates but it is not associated with an overall mortality advantage. However, the treatment effect varies depending on the intervention, the patient population, and the methodological quality of the study.

[Requirement for the structure and function of a nutritional support team]. / Anforderungen an Struktur und Funktion eines Ernährungsteams. Projektgruppe KlinischerErnährung (PROKER).

Procedures in clinical nutrition have gained both invasiveness as well as the complexity. Thus improved education of professionals and their alliance in hospital based nutritional support teams (NST) is demanding. Two forms of collaboration, the "interdisciplinary nutritional committee" and the "department for nutritional therapy", are discussed. It is the goal of this contribution to present structure and tasks of an independently working department for nutritional support therapy. The pertinent areas of activity are composed as followed: clinical nutritional therapy, home nutrition, education, research, and quality management. The team members include the physician, the dietitian, the nurse, the nutritionist, and the pharmacist. The individual tasks as well as the areas of responsibility are presented. We discuss, whether nutritional support teams might be suitable to achieve cost reduction, provided adequate working conditions are available. Issues like "performance related reimbursement" and "NST certification" by health care organizations are discussed. We also elude to the option to merge services with other health care providers in order to built up an inter-disciplinary organization system. We conclude that nutritional support teams have to be prepared to meet hospital needs. Costs/benefit balances have to be assessable and must be documented. Although the effectiveness of selected nutritional support teams was clearly shown, it is the challenge of each individual team to produce proof of effectiveness for itself. Acceptable working conditions, however, should be provided as they have to be considered indispensable to achieve high quality performance.

[Immune function and organ failure. Immunomodulation with nutritional support--an update]. / Immunfunktion und Organversagen. Immunmodulation durch Ernährungssubstrate--"update".

Today, substrates with immunomodulatory effects are not only identified in all groups of macronutrients, but also in the domains of vitamins and traceelements. Mainly they interfere with 3 areas of the immune response: 1. the mucosal barrier function, 2. the cellular defense function, and 3. the local or systemic inflammatory response. Enteral formulas enriched with immune-enhancing diets are already in clinical use to encounter "immunoparalysis" of cellular defense during critical illness. Considering defined outcome variables, indeed, current clinical studies point out some improvements. Using an evidence based approach, a grade A recommendation was proclaimed for its broad clinical use. For defined subgroups of patients, however, presenting with most severe appearances of SIRS and consecutive organ failure, the current concept of enteral immunonutrition remains to be a matter of debate, and the evidence of clinical benefits persist to be questionable.

[Cerebral protection. The role of nutritional therapy]. / Zerebrale Protektion. Stellenwert der Ernährungstherapie.

Prevention of secondary cerebral insults has the highest priority as far as therapeutic interventions of the patient with brain lesions are concerned. Patients with cerebral lesions have to overcome both, cerebral and systemic insults. The intensity of the neuronal injury determines the grade of hypermetabolism. Optimal metabolic and nutritional therapy for patients with cerebral lesions should be accomplished to minimize secondary brain damage. Frequently, the systemic hypermetabolic response is associated with cerebral ischemic metabolism. Therefore systemic blood glucose levels should be less than 150 mg/dl to prevent intracellular anaerobic accumulation of lactate. Individual utilization capacity of substrates is determined by the grade of hypermetabolism. Substrate load has to be adapted to the individual utilization capacity to avoid side effects of nutritional therapy like substrate and volume overload, imbalances of electrolytes as well as enhanced application of excitatoric substrates. In addition, whenever possible enteral nutrition should be applied to profit from reduced bacterial translocation and improved glucose hemostasis. Oxygen radical production and lipid peroxidation are important pathophysiologic mechanisms concerning cerebral lesions. More recent data show reduced antioxidative status in patients with brain injuries which favors lipid peroxidation. Further studies must be carried out to evaluate the potential neuro-protective effect of an antioxidative nutritional regimen in patients with cerebral lesions.

The scientific basis of immunonutrition.

Substrates with immune-modulating actions have been identified among both macro- and micronutrients. Currently, the modes of action of individual immune-modulating substrates, and their effects on clinical outcomes, are being examined. At present, some enteral formulas are available for the clinical setting which are enriched with selected immune-modulating nutrients. The purpose of the present paper is to review the scientific rationale of enteral immunonutrition. The major aspects considered are mucosal barrier structure and function, cellular defence function and local or systemic inflammatory response. It is notable that in critical illness the mucosal barrier and cellular defence are impaired and a reinforcement with enteral immunonutrition is desirable, while local or systemic inflammatory response should be down regulated by nutritional interventions. The results available from clinical trials are conflicting. Meta-analyses of recent trials show improvements such as reduced risk of infection, fewer days on a ventilator, and reduced length of intensive care unit and hospital stay. Thus, a grade A recommendation was proclaimed for the clinical use of enteral immune-modulating diets. Improvement in outcome was only seen when critical amounts of the immune-modulating formula were tolerated in patients classified as being malnourished. However, in other patients with severe sepsis, shock and organ failure, no benefit or even disadvantages from immunonutrition were reported. In such severe conditions we hypothesize that systemic inflammation might be undesirably intensified by arginine and unsaturated fatty acids, directly affecting cellular defence and inflammatory response. We therefore recommend that in patients suffering from systemic inflammatory response syndrome great caution should be exercised when immune-enhancing substrates are involved which may aggravate systemic inflammation.

Recombinant human growth hormone for reconditioning of respiratory muscle after lung volume reduction surgery.

OBJECTIVE: To investigate the effects of recombinant human growth hormone (rHGH) as a "rescue treatment" in an end-stage chronic obstructive pulmonary disease patient after prolonged weaning failure. DESIGN: Descriptive case report. SETTING: Fifteen-bed intensive care unit in a university hospital. PATIENT: A 62-year-old man with end-stage chronic obstructive pulmonary disease and pulmonary emphysema after lung reduction surgery and prolonged weaning failure after long-term mechanical ventilation. INTERVENTIONS: After 42 days of unsuccessful weaning from the respirator, rHGH (27 IU/day, 0.3 IU/kg body weight/day) was administered for 20 days through a subcutaneous injection in addition to standard intensive care. MEASUREMENTS AND MAIN RESULTS: In addition to daily routine laboratory studies, the visceral proteins prealbumin, retinol-binding protein, and transferrin, and nitrogen balance were measured twice a week, as were the thyroid hormones triiodothyronine, thyroxine, and thyroid-stimulating hormone, plasma insulin levels, and the insulin-like growth factor (IGF)-1 binding proteins IGF-BP1 and IGF-BP3. IGF-1 was measured from day 1 to day 4 of rHGH administration. Nutritional support was guided by indirect calorimetry. Additionally, weaning variables such as peak expiratory flow rate and expiratory tidal volume were measured noninvasively. T-piece weaning trials were carried out daily until respiratory muscle fatigue occurred. IGF-1 increased in response to rHGH stimulation, from 103 to 230 microg/mL, within 4 days. The carrier protein IGF-BP3 increased from 126 to 283 mg/L at the end of the study period, and the inhibiting IGF-BP1 decreased initially from 19 to 14 mg/L and then increased until the end of the study to 31 mg/L. Nitrogen balance increased initially from 4.6 to 13.6 g/24 hrs and thereafter decreased until the end of rHGH treatment to 8.3 g/24 hrs. Resting energy expenditure increased from 1800 to 2300 kcal/24 hrs. Peak expiratory flow rate increased from 0.69 to 0.88 L/sec. The expiratory tidal volume showed a slight increase during the study period during the daily decrease of pressure support on the ventilator setting. Respiratory muscular strength increased beginning 10 days after rHGH therapy was started. From this point, T-piece weaning trials could be prolonged almost daily. The patient was extubated successfully on postoperative day 75. CONCLUSIONS: This case report shows that after a prolonged catabolic state and long-term mechanical ventilation, administration of rHGH not only enhances the response of protein metabolism but improves respiratory muscular strength. Therefore, it may reduce the duration of mechanical ventilation in selected patients.