Impact of preoperative serum creatinine on short- and long-term mortality after cardiac surgery: a cohort study.

BACKGROUND: Preoperative renal insufficiency is an important predictor of mortality after cardiac surgery. This retrospective cohort study was designed to identify the optimal cut-off for baseline serum creatinine (bSCr) and estimated glomerular filtration rate (eGFR) to predict survival. Furthermore, we investigated the potential confounding effect of other perioperative risk indicators on short- and long-term survival. METHODS: Data of 9490 cardiac surgical patients were prospectively collected between 1997 and 2008 (follow up to 2010) at the Medical University Vienna. We identified bSCr cut-off values and calculated uni- and multivariate hazard models for short- and long-term survival and compared the results with a validation set from Zurich. The estimated survival curves defined a distinct period of increased mortality until 150 days. RESULTS: Cut-off values of >115 µmol litre(-1) for bSCr and ≤50 ml min(-1) for eGFR were identified. Increased bSCr, associated with higher mortality [hazard ratio (HR) 2.61, 95% confidence interval (CI) 2.43-2.80, P<0.0001], was present in 19.5% of patients and remained predictive for short- (HR 1.59, 95% CI 1.38-1.83, P=0.0027) and long-term survival (HR 1.46, 95% CI 1.32-1.62, P<0.0001) in the multivariate hazard models. A cut-off of >120 µmol litre(-1) for bSCr was determined for the validation set. Decreased eGFR was present in 23.6% (HR 2.86, 95% CI 2.67-3.06, P<0.0001). CONCLUSIONS: In our patients, increased bSCr was an independent predictor of mortality, which may critically influence risk evaluation and perioperative treatment guidance.

Low-dose remifentanil to suppress haemodynamic responses to noxious stimuli in cardiac surgery: a dose-finding study.

BACKGROUND: High-dose remifentanil (1-5 microg kg-1 min-1), commonly used for cardiac surgery, has been associated with muscle rigidity, hypotension, bradycardia, and reduced cardiac output. The aim of this study was to determine an optimal lower remifentanil dose, which should be accompanied by fewer adverse events, that still effectively suppresses haemodynamic responses to typical stressful stimuli (i.e. intubation, skin incision, and sternotomy). METHODS: Total i.v. anaesthesia consisted of a target-controlled propofol (2 microg ml-1) and a remifentanil infusion. Forty patients were allocated to receive either a constant infusion of remifentanil at 0.1 microg kg-1 min-1 or up-titrations to 0.2, 0.3, or 0.4 microg kg-1 min-1, respectively, 5 min before each stimulus. Subsequently, changes in heart rate and mean arterial blood pressure were recorded for 8 min. Increases exceeding 20% of baseline were considered to be of clinical relevance. Patients who exhibited these alterations were termed responders. RESULTS: The number of responders was less with the two higher remifentanil dosages (P<0.05) while propofol target doses could either be kept at the same level or even be reduced without affecting the plane of anaesthesia. Although single phenylephrine bolus had to be applied more frequently in these two groups (P<0.05), no severe haemodynamic depression was observed. CONCLUSIONS: Remifentanil at 0.3 and 0.4 microg kg-1 min-1 in combination with a target-controlled propofol infusion in the pre-bypass period is well tolerated. It appears to mitigate potentially hazardous haemodynamic responses from stressful stimuli equally well as higher doses when compared with data from the literature.

Magnesium moderately decreases remifentanil dosage required for pain management after cardiac surgery.

BACKGROUND: Magnesium is a calcium and an NMDA-receptor antagonist and can modify important mechanisms of nociception. We evaluated the co-analgesic effect of magnesium in the postoperative setting after on-pump cardiac surgery. METHODS: Forty patients randomly received either magnesium gluconate as an i.v. bolus of 0.21 mmol kg(-1) (86.5 mg kg(-1)) followed by a continuous infusion of 0.03 mmol(-1) kg(-1) h(-1) (13.8 mg kg(-1) h(-1)) or placebo for 12 h after tracheal extubation. After surgery, remifentanil was decreased to 0.05 microg kg(-1) min(-1) and titrated according to a pain intensity score (PIS, range 1-6) in the intubated, awake patient and a VAS scale (range 1-100) after extubation. If PIS was > or =3 or VAS > or =30, the infusion was increased by 0.01 microg kg(-1) min(-1); if ventilatory frequency was < or =10 min(-1) it was decreased by the same magnitude. RESULTS: Magnesium lowered the cumulative remifentanil requirement after surgery (P<0.05). PIS > or =3 was more frequent in the placebo group (P<0.05). Despite increased remifentanil demand, VAS scores were also higher in the placebo group at 8 (2 vs 8) and 9 h after extubation (2 vs 7) (P<0.05). Dose reductions attributable to a ventilatory frequency < or =10 min(-1) occurred more often in the magnesium group (17 vs 6; P<0.05). However, time to tracheal extubation was not prolonged. CONCLUSIONS: Magnesium gluconate moderately reduced the remifentanil consumption without serious side-effects. The opioid-sparing effect of magnesium may be greater at higher pain intensities and with increased dosages.

The effects of red-cell scavenging, hemodilution, and active warming on allogenic blood requirements in patients undergoing hip or knee arthroplasty.

UNLABELLED: Since 1993, we have progressively adopted three techniques to reduce transfusion requirements during major orthopedic surgery: red-cell scavenging, acute normovolemic hemodilution, and active patient warming. We retrospectively evaluated all 821 elective hip and knee arthroplasties performed in our institution beginning with July 1993. Target minimal hematocrits were guided by patient ages and cardiovascular status. The first approximately 500-mL blood loss was replaced with crystalloid at a ratio of 3 mL for each milliliter of blood loss. Additional blood loss was replaced with colloid, hemodilution blood (when available), and scavenged red cells (when available). Allogenic transfusions were then administered as necessary to maintain target hematocrits, which were prospectively defined based on the patient ages and cardiovascular health. Univariate analysis was applied initially. Significant predictors of transfusion requirement were subsequently entered into a stepwise multiple regression to account for confounding factors, including age, type of anesthesia (regional versus general) and type of surgery (primary versus hardware replacement). Postoperative hemoglobin concentrations were similar over the years of study and among the patients given each treatment. During the study period, allogenic blood requirements decreased from 1.3 +/- 1.7 U/patient to 0.6 +/- 1.4 U/patient (mean +/- SD). Both univariate and regression analyses indicated that each treatment significantly reduced transfusion requirements (P < 0.05). We conclude that red-cell scavenging, hemodilution, and active cutaneous warming each reduce allogenic blood requirements during hip and knee arthroplasties. IMPLICATIONS: We retrospectively evaluated three strategies to reduce overall blood loss: red-cell scavenging, acute normovolemic hemodilution, and active patient warming. During the study period, allogenic blood requirements decreased by a factor of 2. Each treatment contributed to this reduction. We therefore conclude that each treatment reduces allogenic blood requirements during hip and knee arthroplasties.

Stimulation of human thyroid growth via the inhibitory guanine nucleotide binding (G) protein Gi: constitutive expression of the G-protein alpha subunit Gi alpha-1 in autonomous adenoma.

The alpha subunits of the stimulatory and inhibitory G proteins, Gs alpha and Gi alpha, activate transmembrane-signaling systems involved in the control of cell proliferation. We have investigated the pattern of expression of Gi alpha subtypes and Gi alpha-mediated proliferative responses in the human thyroid. Human thyroid membranes contain two subtypes of Gi alpha, Gi alpha-1 and Gi alpha-2, as assessed by using specific antibodies. The expression of Gi alpha-1 is under tight control by thyrotropin in vivo and in primary cultures of thyroid epithelial cells. In contrast, Gi alpha-1 is expressed in the absence of thyrotropin in thyroid autonomous adenoma, an endocrine-active tumor, and its levels are not regulated by thyrotropin in thyroid epithelial cells prepared from these tumors. If thyroid epithelial cells are treated with pertussis toxin to block signal transduction via Gi, the mitogenic response to serum factors is reduced. These observations demonstrate that Gi subtypes transmit growth stimuli in the human thyroid. The constitutive expression of Gi alpha-1 in autonomous adenoma may allow for the unregulated stimulation of thyroid cell proliferation by a yet unidentified signaling pathway and, thus, be causally related to autonomous growth of thyroid cells.

Gi alpha-1 expression in the human thyroid is regulated by TSH: loss of regulation in thyroid autonomous adenoma.

The molecular mechanisms underlying the development of endocrine active thyroid tumors are poorly understood. These tumors produce excess thyroid hormone, which then suppresses TSH (thyroid stimulating hormone) production. In the present report, we show that the expression of Gi alpha-1 is under control of TSH in the normal human thyroid. In contrast Gi alpha-1 escapes TSH control in autonomous adenoma and thus is constitutively expressed. Since receptor-mediated activation of Gi controlled pathways is known to elicit a proliferative response in several cell types, we propose that in thyroid adenomas the unregulated constitutive expression of Gi alpha-1 is causally related to the autonomous growth.