Groote Schuur Hospital neurosurgical intensive care unit: A 2-year review of admission characteristics.

Background: At Groote Schuur Hospital (GSH), the neurosurgical intensive care unit (NsICU) is a 6-bed unit headed by a specialist neurosurgeon with extensive experience in neurocritical care, working in close collaboration with intensivists from the Division of Critical Care. There is currently no detailed analysis of the demographics, diagnosis and management of patients admitted to the NsICU at GSH. Objectives: To provide a detailed descriptive analysis of the demographics, diagnosis and management of patients admitted to the NsICU at GSH from 1 January 2020 to 31 December 2021. Methods: A retrospective descriptive analysis was done of patients who received treatment in the NsICU from 1 January 2020 to 31 December 2021. Results: A total of 685 patients were admitted to the unit over a 2-year period, with a male preponderance (68.2%). The average age was 42.5 (standard deviation (SD) 17.2) years. The most common neurosurgical diagnoses were traumatic brain injuries (39.6%), brain tumours (22.6%) and aneurysmal subarachnoid haemorrhages (9.9%). Emergency admissions comprised 76.6% of the total and 86.7% of patients were admitted postoperatively. Three hundred and seventy-two patients (54.3%) required mechanical ventilation, 132 (19.3%) required both an intracranial pressure (ICP) monitor and brain tissue oxygenation monitor, 86 (12.5%) needed placement of an external ventricular drain, 50 (7.3%) needed placement of a tracheostomy tube and 16 (2.3%) needed placement of an ICP monitor only. The average duration of stay was 5.5 (1.3) days and NsICU mortality over 2 years was 11.1%. Conclusion: The NsICU at GSH manages predominantly male trauma patients and a significant number of admitted patients require specialised invasive intracranial monitoring. Contribution of the study: This is the first in-depth analysis of patients managed in a dedicated neurosurgical intensive care unit in South Africa. The work defines the patient population, neurosurgical pathologies and service level requirements that would likely be encountered by teams building a similar service.

Outcomes of patients with COVID-19 acute respiratory distress syndrome requiring invasive mechanical ventilation admitted to an intensive care unit in South Africa.

BACKGROUND: Up to 32% of patients with COVID-19 pneumonia may require intensive care unit (ICU) admission or mechanical ventilation. Data from low- and middle-income countries on COVID-19 acute respiratory distress syndrome (ARDS) are limited. Groote Schuur Hospital in Cape Town, South Africa, expanded its intensive care service to support patients with COVID-19 ARDS requiring invasive mechanical ventilation (IMV). OBJECTIVES: To report on patients' characteristics and outcomes from the first two pandemic waves. METHODS: All patients with COVID-19 ARDS admitted to the ICU for IMV were included in this prospective cohort study. Data were collected from 5 April 2020 to 5 April 2021. RESULTS: Over the 12-month study period, 461 patients were admitted to the designated COVID-19 ICU. Of these, 380 met the study criteria and 377 had confirmed hospital discharge outcomes. The median (range) age of patients was 51 (17 - 71) years, 50.5% were female, and the median (interquartile range (IQR)) body mass index was 32 (28 - 38) kg/m2. The median (IQR) arterial oxygen partial pressure to fractional inspired oxygen (P/F) ratio was 97 (71 - 128) after IMV was initiated. Comorbidities included diabetes (47.6%), hypertension (46.3%) and HIV infection (10.5%). Of the patients admitted, 30.8% survived to hospital discharge with a median (IQR) ICU length of stay of 19.5 (9 - 36) days. Predictors of mortality after adjusting for confounders were male sex (odds ratio (OR) 1.74), increasing age (OR 1.04) and higher Sequential Organ Failure Assessment (SOFA) score (OR 1.29). CONCLUSIONS: In a resource-limited environment, the provision of IMV support in the ICU achieved 30.8% hospital survival in patients with COVID-19 ARDS. The ability to predict survival remains difficult given this complex disease.

The organisational response of a hospital critical care service to the COVID-19 pandemic: The Groote Schuur Hospital experience.

Background: There are limited data about the coronavirus disease-19 (COVID-19)-related organisational responses and the challenges of expanding a critical care service in a resource-limited setting. Objectives: To describe the ICU organisational response to the pandemic and the main outcomes of the intensive care service of a large state teaching hospital in South Africa. Methods: Data were extracted from administrative records and a prospective patient database with ethical approval. An ICU expansion plan was developed, and resource constraints identified. A triage tool was distributed to referring wards and hospitals. Intensive care was reserved for patients who required invasive mechanical ventilation (IMV). The total number of ICU beds was increased from 25 to 54 at peak periods, with additional non-COVID ICU capacity required during the second wave. The availability of nursing staff was the main factor limiting expansion. A ward-based high flow nasal oxygen (HFNO) service reduced the need for ICU admission of patients who failed conventional oxygen therapy. A team was established to intubate and transfer patients requiring ICU admission but was only available for the first wave. Results: We admitted 461 COVID-19 patients to the ICU over a 13-month period from 5 April 2020 to 5 May 2021 spanning two waves of admissions. The median age was 50 years and duration of ICU stay was 9 days. More than a third of the patients (35%; n=161) survived to hospital discharge. Conclusion: Pre-planning, leadership, teamwork, flexibility and good communication were essential elements for an effective response. A shortage of nurses was the main constraint on ICU expansion. HFNO may have reduced the requirement for ICU admission, but patients intubated after failing HFNO had a poor prognosis. Contributions of the study: We describe the organisational requirements to successfully expand critical care facilities and strategies to reduce the need for invasive mechanical ventilation in COVID-19 pneumonia. We also present the intensive care outcomes of these patients in a resource-constrained environment.

Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis.

BACKGROUND: The diagnosis of smear-negative pulmonary tuberculosis (TB) is problematic. There are limited data on the profile of alveolar TB antigen-specific T cells, and their utility for the rapid immunodiagnosis of pulmonary TB is unclear. METHODS: Antigen-specific interferon gamma (IFNgamma) responses to the RD-1 antigens ESAT-6 and CFP-10 (T-SPOT.TB and QuantiFERON-TB-Gold-In-Tube), heparin-binding haemagglutinin and purified protein derivative were evaluated, using alveolar lavage cells, in 91 consecutively recruited South African patients suspected of having TB. RESULTS: Of 85 evaluable patients (29% HIV+), 24, 11, 48 and 2 had definite TB, probable TB, non-TB and an uncertain diagnosis, respectively. Between 34% (T-SPOT.TB) and 41% (QuantiFERON-TB-Gold-In-Tube) of all test results were inconclusive. Failure of the positive control was significantly higher with the QuantiFERON-TB-Gold-In-Tube than with T-SPOT.TB (85% vs 46% of inconclusive results; p = 0.001). Using staphylococcal enterotoxin B, compared with phytohaemagglutinin, substantially reduced failure of the positive control (25% to 3%; p = 0.02). In evaluable samples, when the definite and non-TB groups were used for outcome analysis, the percentage sensitivity, specificity, positive predictive value and negative predictive value for T-SPOT.TB (> or = 20 spots/million alveolar mononuclear cells) and QuantiFERON-TB-Gold-In-Tube (0.35 IU/ml) were 89, 94, 89 and 94% (n = 55) and 55, 86, 77 and 69% (n = 46), respectively. Rapid diagnosis of TB was achieved more frequently with T-SPOT.TB than with smear microscopy (14/24 (58%) vs. 7/24 (29%) of definite TB cases; p = 0.02). Heparin-binding haemagluttinin and purified protein derivative alveolar lymphocyte IFNgamma responses had poor performance outcomes. CONCLUSION: Provided evaluable results are obtained, the RD-1, but not the heparin-binding haemagglutinin or purified protein derivative, alveolar lymphocyte IFNgamma ELISPOT response is a useful rapid immunodiagnostic test for TB. However, test utility in high-burden settings may be limited by the high proportion of inconclusive results.

Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis.

The clinical utility of antigen-specific interferon (IFN)-gamma release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification. We compared the diagnostic utility of unstimulated pleural IFN-gamma levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.(R)TB, QuantiFERON(R)-TB Gold In-tube), purified protein derivative (PPD) and heparin-binding haemagglutinin (HBHA)) in 78 South African TB suspects. Test results were compared against a clinical score and a reference standard. Out of 74 evaluable subjects 48, seven and 19 had definite, probable and no TB, respectively. 11 (15%) out of 74 pleural samples (nine (19%) out of 48 of the definite TB cases) had total cell counts that were inadequate for T-cell processing. In the remaining 63 samples, the sensitivity, specificity, positive predictive value and negative predictive value of different diagnostic methods were as follows. Maximal bioclinical score: 54, 89, 92 and 43%, respectively; T-SPOT.(R)TB: 86, 60, 84 and 64%, respectively; QuantiFERON(R)-TB Gold In-tube: 57, 80, 87 and 44%, respectively; HBHA-specific IGRA: 59, 31, 64 and 27%, respectively; PPD-specific IGRA: 81, 40, 76 and 46%, respectively; and pleural fluid unstimulated IFN-gamma: 97, 100, 100 and 94%, respectively. Unstimulated IFN-gamma was the most accurate test for distinguishing TB from non-TB effusions in a high-burden setting. The antigen-specific T-cell IGRAs were limited by suboptimal accuracy and the inability to isolate sufficient mononuclear cells to perform the assay.

The effects of hemorrhage and sodium depletion on plasma concentrations of angiotensin II and [des-Asp1]angiotensin II in the rat.

Plasma concentrations of angiotensin II (PAII) and [des-Asp1]angiotensin II (Pdes-Asp1-AII) were measured before and after hemorrhage and acute and chronic depletion of sodium. Graded hemorrhage increased PAII from 30 +/- 5 to 220 +/- 41 and 989 (526-1290) pmol/liter and Pdes-Asp1-AII from 47 +/- 11 to 216 +/- 72 and 532 +/- 178 pmol/liter. Furosemide increased PAII from 26 +/- 4 to 178 +/- 37 but did not change Pdes-Asp1-AII (31 +/- 3 to 31 +/- 4 pmol/liter). Deprivatin of dietary sodium increased PAII from 25+/- 6 to 136+/- 22 pmol/liter and Pdes-Asp1-AII from 41 +/- 4 to 71 +/- 15 pmol/liter. The ratio of PAII to Pdes-Asp1-AII was increased by all three stimuli (P < 0.05 to P < 0.001). Pdes-Asp1-AII II is unlikely to mediate the effects of hemorrhage and changes in sodium balance on aldosterone secretion in the rat.

Cation-dependent and cation-independent stages in regulation of the vascular angiotensin receptor after alteration of sodium balance in the rat.

The role of cations in vascular angiotensin receptor regulation has been investigated by radioligand receptor assay using a cell membrane fraction derived from mesenteric arterial muscle of the rat. In arterial membrane fractions from normal rats, the apparent receptor density varied with the ambient [Ca++] over the range, 0-10 mM. Receptor densities of 50 +/- 4, 102 +/- 4, and 156 +/- 5 fmol/mg membrane protein were obtained in low (0 mM), normal (4.8 mM), and high (25 mM) [Ca++], respectively. After 2 days of sodium loading, sodium depletion, and converting enzyme blockade altered receptor densities were detected in normal assay but not in high [Ca++] or low [Ca++], indicating changes in the relationship between [Ca++] and apparent receptor density. Similar results were obtained after 12 days of sodium loading or converting enzyme blockade. After 12 days of sodium depletion, there was no difference in receptor density between normal and high [Ca++] (44 +/- 5 fmol/mg protein) and the value obtained in low [Ca++] (27 +/- 2 fmol/mg protein) was significantly below that for all other groups. No change in receptor affinity was observed. These results suggest that there are two stages in vascular angiotensin receptor regulation; an initial masking-unmasking process which involves Ca++, and with prolonged agonist occupancy, an actual loss of receptors.

[des-Asp1]angiotensin II in the dog: blood levels and effect on aldosterone.

Circulating levels of [des-Asp1]angiotensin II ([des-Asp1]-AII), angiotensin II (AII), and aldosterone were measured in five conscious beagle dogs before and during iv infusion of [des-Asp1]AII at rates of 3, 6, 12, and 24 ng/kg/min. The animals were studied after 4 days on a normal sodium and potassium diet and again after a period of sodium depletion accomplished by iv furosemide (2-5 mg/kg) and 4 days of low sodium diet (2-5 mmol/day). Compared to the normal sodium diet, sodium depletion resulted in increases in the plasma levels of aldosterone from 10 +/- 2 (SE) to 66 (16-116) ng/100 ml of AII from 16 +/- 4 to 52 +/- 13 pmol/liter and of [des-Asp1]AII from 2 +/- 0.7 to 12 +/- 4 nmol/liter. Incremental infusions of [des-Asp1]AII in the sodium replete state resulted in progressive increases in the plasma levels of aldosterone in all dogs. In comparison with a previous study in which dogs were infused with AII, it was apparent that [des-Asp1]AII was equally or slightly more potent in stimulating aldosterone and had a higher metabolic clearance rate than AII. [des-Asp1]AII stimulated aldosterone in four of the five sodium-depleted dogs but no steepening of the [des-Asp1]AII/aldosterone dose-response curves was apparent. These results do not support the hypothesis that circulating [des-Asp1]AII mediates the effect of AII on aldosterone in the dog.

The concentration of angiotensins I and II in blood from the pulmonary artery and left ventricle of man.

The concentrations of angiotensin I (AI) and II (AII) were determined by radioimmunoassay in blood from the main pulmonary artery (MPA) and left ventricule (LV) of ten subjects with rheumatic valvular heart disease. The levels of AI were consistently higher in MPA plasma (21.8+/-2.4 pmol/1) than in LV plasma (14.7+/-2.0 pmol/1), paired t, P less than 0.001. The levels of AII were consistently lower in MPA plasma (21.8+/-4.7 pmol/1) than in LV plasma (33.8+/-7.2 pmol/1), paired t, P less than 0.001. The AII antiserum cross-reacted with three metabolites of the hormone, [des-Asp1]angiotensin II, [des-(Asp1, Arg2)angiotensin II [des-(Asp1, Arg2 Val,3]angiotensin II. To characterize the nature of circulating AII immunoreactive material, paper chromatography was used to separate AII from its immunoreactive metabolites. The results showed that 84-100% of the AII immunoreactive material from both MPA and LV plasma chromatographed with the mobility of authentic angiotensin II. The mean pulmonary conversion of endogenous AI was 33+/-4.8% and the net extraction of AII by peripheral tissues was 33+/-4.1%.

Effects of furosemide on glomerular filtration rate and clearance of practolol, digoxin, cephaloridine, and gentamicin.

Furosemide was shown to decrease inulin clearance in 20 of 27 normal subjects. The depression in inulin clearance occurred in both water-loaded and non-water-loaded subjects. The renal clearance of practolol, but not digoxin, was reduced when furosemide was given. The average total plasma clearances of gentamicin and of cephaloridine over a 6-hr period were decreased after furosemide. The reduced clearances of the antibiotics were associated with higher plasma levels, the increase in antibiotic concentration being as much as 100% at 1 hr after an intravenous bolus injection.

Angiotensin II levels, hemodynamics, and sympathoadrenal function after low-dose captopril in heart failure.

The angiotensin converting enzyme inhibitor captopril improves the altered hemodynamics in many patients with chronic heart failure, but the first dose may precipitate hypotension. Ten patients with chronic heart failure were studied, nine with high plasma concentrations of renin and one with a low concentration. Frequent measurements of plasma concentrations of angiotensin II, renin, and catecholamines were made over 60 minutes after a small dose (6.25 mg) of captopril and related to concurrently measured hemodynamic variables. Captopril caused a decrease in systemic and pulmonary artery pressure and an increase in cardiac index, and these changes coincided with reductions in the plasma concentrations of angiotensin II and increases in plasma concentrations of renin. The hemodynamic changes were accompanied by reductions in the plasma concentrations of norepinephrine but transient increases in plasma concentrations of epinephrine in patients in whom vasomotor syncope developed. The patient with a low plasma renin concentration showed little hemodynamic response to the drug. It is concluded that vasomotor syncope occurs quite frequently in patients with severe chronic heart failure after captopril in a small dose and is associated with a selective increase in epinephrine secretion from the adrenal medulla.

Potassium influx into erythrocytes in essential hypertension.

Sodium plus potassium (Na+K) cotransport in erythrocytes of patients with essential hypertension has mainly been studied elsewhere by measuring net outward frusemide-sensitive Na and K movements. We compared K influx (tracer 86 Rubidium) in control subjects and hypertensives who had never previously been treated for hypertension. The cotransport K influx rates in controls and hypertensives were 0.44 +/- 0.02 (mumol/ml cells/h; mean +/- s.e.; n = 20) and 0.67 +/- 0.06 (mumol/ml cells/h; mean +/- s.e.; n = 23) respectively. The active influxes were 1.03 +/- 0.03 and 2.06 +/- 0.13 (mumol/ml cells/h; mean +/- s.e.) respectively. The variance of both parameters was significantly greater in the hypertensive group but, taking this into account, the differences were significant (P less than 0.01).

Regulation of platelet receptors for angiotensin II in man.

The effects of changes in dietary intake of sodium and potassium on 125I-angiotensin II binding to platelets were studied in normal subjects. We also defined binding to platelets from patients with essential hypertension and subjects with normal blood pressure. Restriction of sodium intake in normal subjects resulted in a decrease in the number of receptor sites from 6.2 +/- 0.3 sites/cell to 4.1 +/- 0.4 sites/cell (P less than 0.01) but there were no changes in affinity as measured by the Kd. Over a range of sodium intakes from 15 to 200 mmol/day there was a negative correlation between plasma concentration of angiotensin II and receptor site concentration (rs = 0.57, P less than 0.01). Changes in dietary potassium did not affect angiotensin II binding. Angiotensin II binding was also measured in 10 patients with essential hypertension (mean blood pressure [BP] 178/107 mmHg, plasma concentrations of renin [PRC] 12 +/- 2 microU/ml and angiotensin [pANG] II 14 +/- 2 pg/ml) and 10 subjects with normal blood pressure (mean BP 112/74 mmHg, PRC 13 +/- 2 microU/ml, pANG II 13 +/- 2 pg/ml). In the hypertensive patients, binding capacity and affinity (Kd = 5.0 +/- 0.6 X 10(-10) M, 5.7 +/- 0.8 sites/cell) were similar to those in the normotensive subjects (Kd = 4.9 +/- 0.8 X 10(-10) M, 5.4 +/- 0.5 sites/cell). Changes in sensitivity to angiotensin II in essential hypertension may not be determined at receptor level. Angiotensin II receptors in platelets respond to changes in sodium intake like receptors in arterial muscle.

Effects of potassium on sodium balance, renin, noradrenaline and arterial pressure.

To determine the effects of potassium on blood pressure and factors affecting blood pressure, we conducted a randomized, placebo controlled trial of a potassium chloride-based substitute for table salt in 23 patients with mild to moderate essential hypertension. In addition, the effects of potassium chloride on sodium balance were studied in 10 normal subjects. Potassium loading with 100 mmol/day over five days in these normal subjects caused a cumulative negative sodium balance of 138 +/- 35 mmol, similar in degree to that achieved by severe dietary sodium restriction. However, two weeks of potassium treatment (100 mmol/day) in patients with essential hypertension did not lower blood pressure (BP) either in the supine or upright positions (potassium treatment: mean BP 108 +/- 3 lying and 113 +/- 3 mmHg standing; placebo treatment: mean BP 109 +/- 3 lying and 115 +/- 3 mmHg standing). Patients found it difficult to tolerate the potassium-based salt substitute in the dose given. We conclude that it is premature to recommend an increase in potassium chloride intake as treatment for raised blood pressure.

Renal artery stenosis managed by Palmaz stent insertion: technical and clinical outcome.

OBJECTIVE: To assess the technical and clinical outcome of Palmaz renal artery stent insertion in patients with renal artery stenosis. DESIGN: Twenty-nine patients with radiological evidence of renal artery stenosis and hypertension (16 patients, mean +/- SD diastolic blood pressure 100.5 +/- 8.16 mmHg) and/or renal impairment (17 patients, mean +/- SD serum creatinine 376 +/- 169 mu mol/l) were referred for radiological intervention. Of these, 22 had ostial atheromatous lesions, six had atheromatous non-ostial lesions and one patient had fibromuscular dysplasia. Palmaz stent insertion was performed where either previous or concomitant percutaneous transluminal renal angioplasty (PTRA) had been unsuccessful. Technical success was defined primarily as <30% residual stenosis. A prospective radiological and clinical follow-up was performed and the results compared with the outcome following PTRA alone in a similar group of patients from our centre. RESULTS: Immediate technical success was achieved in all 29 patients. Follow-up angiography in 24 patients after a mean of 7 months showed restenosis in four patients. The hypertension was not 'cured' in any patient; a blood pressure fall was observed in seven patients (44%) and no change in the remaining nine subjects (56%). Renal function improved in four patients (24%), two of whom had angiotensin converting enzyme inhibitor-exacerbated renal impairment. This compares with an immediate technical success of 81% for PTRA alone, with cure in 50% and improvement in 32% of patients with hypertension and improvement in renal function in 64.7% of patients with renal impairment. CONCLUSIONS: Palmaz renal artery stent insertion has a higher technical success rate than PTRA, but the clinical improvement is disappointing in our patient population.

Relation of blood pressure with body and plasma electrolytes in Conn's syndrome.

Thirty-four patients with untreated Conn's syndrome were studied in a metabolic ward. The final diagnosis in each case was based on the finding and removal of an adrenal cortical adenoma with histological features typical of the disorder. Compared with 34 age and sex-matched normal controls the untreated patients had increased plasma aldosterone concentration, increased blood pressure (183/112 mmHg), increased exchangeable sodium (116.7% of normal), hypokalaemia and increased plasma sodium concentration. Exchangeable potassium was lower than normal and plasma concentrations of active renin, total renin and angiotensin II were lower than normal mean values. Arterial pressure correlated significantly and positively with plasma and exchangeable sodium and there was a significant negative correlation with plasma potassium concentration. Partial regression analysis showed that the relation of exchangeable sodium with blood pressure did not depend on age or renal function but that the relation of blood pressure and plasma potassium could be attributed to the correlation of exchangeable sodium and blood pressure. Multiple regression analysis suggested that exchangeable and plasma sodium were the most important determinants of blood pressure in untreated patients. Spironolactone, amiloride and surgical removal of the adenoma corrected the electrolyte abnormality and usually lowered blood pressure. The fall in exchangeable sodium was related to the fall in blood pressure. The pattern of correlation found by multiple regression analysis in postoperative patients was similar to that in normal subjects. The findings are relevant to some of the mechanisms proposed for the hypertension of mineralocorticoid excess.

Potentiation of adrenaline-induced platelet aggregation by angiotensin II.

The effects of angiotensin II (ANG II) alone and in combination with other agonists on human platelet aggregation, thromboxane B2 (TxB2) and cytosolic [Ca2+]i were investigated. ANG II (10(-11) - 10(-7) M) alone had no direct effect on aggregation, TxB2 production or [Ca2+]i after short- (less than 2 min) or long-term (30 min) incubation. In contrast, low concentrations of ANG II (10(-11) M) enhanced adrenaline-induced platelet aggregation but high concentrations (10(-7) M) had an inhibitory effect. Moreover, ANG II (10(-11) - 10(-7) M) augmented platelet responses to the TxA2 mimetic, U44069. Pretreatment of platelets with flurbiprofen abolished this facilitatory effect of ANG II on adrenaline- but not on U44069-induced platelet aggregation. These results suggest that ANG II stimulation of agonist-induced platelet activation may be due to potentiation of the effects rather than the synthesis of TxA2.

Severe hypotension with bradycardia during renin inhibition with H142 in sodium deplete man.

A healthy sodium depleted subject received, on separate occasions, intravenous infusions of the renin inhibitor H142 at doses of 1.0, 2.5 and 5.0 mg/kg/h. The two lower doses of H142 produced dose-dependent reduction of both systolic and diastolic pressure associated with an increase in heart rate. The highest dose of H142 produced profound hypotension and bradycardia, both during drug infusion in the supine position, and again later, on return to standing, after H142 was stopped. An increase in plasma adrenaline, but not noradrenaline, was associated with this dose of H142. The subject differed from others studied in a randomised controlled trial of H142 at doses of 1.0 and 2.5 mg/kg/h in having the highest basal circulating plasma angiotensin II concentrations during sodium depletion, and in developing a clear reduction in systolic as well as diastolic pressure. The profound hypotensive response at the highest dose of H142 may represent an idiosyncratic response to the drug. Alternatively, and perhaps more likely, it may be a result of a reduction of angiotensin II concentrations in plasma or other tissues, with loss of arteriolar constriction, loss of facilitation of sympathetic activity, withdrawal of vagal inhibition, dilatation of capacitance vessels, or a combination of these events. Subsequent activation of the Bezold-Jarisch reflex is a possibility. The late fall in blood pressure, after H142 was stopped, and when circulating plasma angiotensin II concentrations had returned to normal, suggests that this response may have involved an effect of the inhibitor on renin in a site other than blood.

Transsphenoidal surgery for Cushing's disease: outcome in patients with a normal magnetic resonance imaging scan.

OBJECTIVE: Transsphenoidal surgery for Cushing's disease from a pituitary adenoma is an effective and safe treatment. Definitive preoperative diagnosis of Cushing's disease caused by a pituitary adenoma is often difficult, particularly in patients with normal imaging studies and a normal sella turcica. We present the outcome of transsphenoidal surgery in patients with presumed Cushing's disease and a normal pituitary magnetic resonance imaging scan. METHODS: Between January 1992 and December 1997, 105 patients underwent transsphenoidal surgery for Cushing's disease at our institution. The criteria for inclusion in this study were clinical and biochemical studies strongly suggestive of Cushing's disease, a normal magnetic resonance imaging scan with normal sella and sellar contents, no previous pituitary surgery, and transsphenoidal surgery performed at this institution. Eighteen patients fulfilled these criteria, and their results were analyzed retrospectively. RESULTS: The average age of the patients was 47.8 years; there were 13 women and 5 men. Inferior petrosal sinus sampling with and without corticotropin-releasing hormone stimulation was performed in 16 patients with correct localization of the lesion in 13 (81%). During surgery, the surgeon identified and removed 17 pituitary tumors; 15 patients had selective adenomectomies, one had a hemihypophysectomy, and two had total hypophysectomies. Thirteen discrete adrenocorticotropic hormone-secreting adenomas were proven histologically, and one pituitary gland had diffuse involvement with tumor. Complications occurred in five patients. Sixteen patients who were followed up for an average of 21.6 months had sustained remission, 12 of whom were profoundly hypocortisolemic immediately after surgery. CONCLUSION: In patients with Cushing's disease and a normal magnetic resonance imaging scan, an experienced surgeon can perform transsphenoidal surgery resulting in effective removal of very small microadenomas, with clinical and biochemical remission in the majority. Inferior petrosal sinus sampling is helpful in localizing the adenoma.

Complications in a contemporary series of patients who underwent transsphenoidal surgery for Cushing's disease.

OBJECT: Transsphenoidal surgery is the usual treatment of choice for adrenocorticotropic hormone-secreting pituitary adenomas associated with Cushing's disease. In this paper the authors investigate the complications of transsphenoidal surgery in the treatment of a contemporary series of patients with Cushing's disease. METHODS: Between January 1992 and December 1997, 105 patients with Cushing's disease underwent transsphenoidal surgery at the University of Virginia Health Sciences Center. A retrospective analysis of the complications was conducted, and the mortality rate was found to be 0.9% and permanent morbidity was 1.8%. The overall number of complications was 14 (13.3%), which included seven complications directly related to surgery; one instance of permanent diabetes insipidus; one syndrome of inappropriate secretion of antidiuretic hormone; and five medical complications (four patients developed deep vein thrombosis and one developed pneumonia). CONCLUSIONS: Transsphenoidal surgery for Cushing's disease has a higher complication rate than that for pituitary adenomas in general. This is primarily related to a greater number of medical complications, most notably deep vein thrombosis, resulting from the generally debilitated state of most patients with Cushing's disease. In view of the high incidence of deep vein thrombosis in these patients, prophylaxis for thromboembolism during the perioperative period is recommended.