Nociceptive activation in spinal cord and brain persists during deep general anaesthesia.

BACKGROUND: In clinical practice, analgesic drug doses applied during general anaesthesia are considered sufficient when clinical responses (e.g. movement, blood pressure and heart rate elevations) are suppressed during noxious stimulation. We investigated whether absent clinical responses are indicative of suppressed spinal and brain responsiveness to noxious stimulation in anaesthetised subjects. METHODS: Ten healthy volunteers were investigated during deep propofol anaesthesia supplemented with increasing doses of remifentanil in a stepwise manner. Noxious electrical stimuli at an intensity comparable with surgical stimulation were repeatedly administered at each targeted remifentanil concentration. During stimulation, we monitored both clinical responses (blood pressure, heart rate, and movement) and neuronal responses. Neuronal responses were assessed using functional magnetic resonance imaging, spinal reflex responses, and somatosensory evoked potentials. RESULTS: This monitoring combination was able to faithfully detect brain and spinal neuronal responses to the noxious stimulation. Although clinical responses were no longer detected at analgesic dosages similar to those used for general anaesthesia in clinical practice, spinal and brain neuronal responses were consistently observed. Opioid doses that are significantly larger than is usually used in clinical practice only reduced neuronal responses to 41% of their maximal response. CONCLUSIONS: Nociceptive activation persists during deep general anaesthesia despite abolished clinical responses. Absent clinical responses are therefore not indicative of absent nociception-specific activation. Thus, commonly accepted clinical responses might be inadequate surrogate markers to assess anti-nociception during general anaesthesia. Further research is required to investigate whether persistent nociception causes adverse effects on patient outcome.

Monitoring of the responsiveness to noxious stimuli during sevoflurane mono-anaesthesia by using RIII reflex threshold and bispectral index.

BACKGROUND: We investigated the accuracy of the (normalized) RIII reflex threshold, the bispectral index (BIS), and the end-tidal sevoflurane concentration for predicting movement responses during mono-anaesthesia using sevoflurane. METHODS: Fourteen male subjects were included. Each received a sevoflurane mono-anaesthesia for which the end-tidal concentration was increased in steps of 0.2 vol% every 10 min. Every 5 min, the reactions to noxious stimuli (10 s trapezius squeeze and 30 s 80 mA tetanic stimulus) were tested. The administration of sevoflurane was halted after no movement reactions occurred for three concentration steps. RIII reflex threshold and BIS were recorded continually in all subjects. RESULTS: Thirteen subjects completed the study. The prediction probabilities for movement reactions to the noxious stimuli were 0.79 for the BIS, 0.91 for the RIII threshold, and 0.89 for the end-tidal sevoflurane concentration (PKDMACRO-Statistics: BIS vs RIII, P<0.05; BIS vs C(sevo), P<0.05; RIII vs C(sevo), P>0.05). All population prediction probability values differed significantly from 0.5 (P<0.01, PKDMACRO). CONCLUSIONS: All three instruments can be used for a prediction of movement responses to a noxious stimulus under sevoflurane mono-anaesthesia with an accuracy exceeding prediction by chance. The accuracy of the BIS to predict these responses appears to be lower compared with the RIII reflex threshold or the end-tidal sevoflurane concentration.

Recombinant hirudin (lepirudin) provides safe and effective anticoagulation in patients with heparin-induced thrombocytopenia: a prospective study.

BACKGROUND: The immunological type of heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced thrombocytopenia. This study evaluated the efficacy of recombinant hirudin (r-hirudin or lepirudin), a potent thrombin inhibitor, for anticoagulation in patients with confirmed HIT. METHODS AND RESULTS: Eighty-two patients in this prospective, multicenter study received 1 of 4 intravenous r-hirudin regimens: A1, HIT patients with thrombosis (n=51), 0.4-mg/kg bolus and then 0.15 mg. kg-1. h-1; A2, HIT patients with thrombosis receiving thrombolysis (n=5), 0. 2-mg/kg bolus and then 0.1 mg. kg-1. h-1; B, HIT patients without thrombosis (n=18), 0.1 mg. kg-1. h-1; and C, during cardiopulmonary bypass surgery (n=8), 0.25-mg/kg bolus and then 5-mg boluses as needed. Response criteria were increase in platelet count by >/=30% to >10(9)/L and activated partial thromboplastin time (aPTT) values 1.5 to 3.0 times baseline values achieved with a maximum of 2 dose increases. No placebo control was used for ethical reasons. Outcomes of a subset of r-hirudin-treated patients who met predefined inclusion criteria (n=71) were compared with those of a historical control group (n=120) for combined and individual incidences of death, amputations, new thromboembolic complications, and incidences of bleeding. Platelet counts increased rapidly in 88.7% of r-hirudin-treated patients with acute HIT. In regimens A1 and A2, the 25% and 75% quartiles of the aPTT were within the target range at all but 1 time point. The incidence of the combined end point (death, amputation, new thromboembolic complications) was significantly reduced in r-hirudin patients compared with historical control patients (P=0.014). During first selected treatment, the adjusted hazard ratio for r-hirudin patients versus historical control was 0.279 (95% CI, 0.112 to 0.699; P=0.003). Bleeding rates were similar in both groups. CONCLUSIONS: r-Hirudin treatment is associated with a rapid and sustained recovery of platelet counts, sufficient aPTT prolongations, and true clinical benefits for patients with HIT.