Incidence of cardiovascular complications in knee arthroplasty patients before and after implementation of a ropivacaine local infiltration analgesia protocol: A retrospective study.

BACKGROUND: Local infiltration analgesia (LIA) during total knee arthroplasty has been shown to give statistically significant reduction in post-operative pain. The effects of using high volumes of ropivacaine combined with adrenaline as LIA on cardiovascular parameters in knee replacement have not been described before. The objective of this study was to investigate the cardiovascular safety of ropivacaine as part of high volume local infiltration analgesia (LIA) in total knee replacement surgery. METHODS: This is a retrospective observational comparative cohort study conducted in two independent cohorts, one treated without and one treated with a local infiltration analgesia protocol, containing a total of 744 patients with a mean age of 68years (42 to 89) and 68years (21 to 88) respectively with a follow-up of 12months. RESULTS: No statistical difference in bradycardia during surgery, post-operative cardiovascular complications, and mortality was found after use of LIA. A statistically significant lower incidence of hypotension was found in the LIA group (P<0.01). This result has to be interpreted with care, due to the use of adrenaline in the LIA mixture, which could mask possible hypotension. No statistical difference was found in the occurrence of hypertension or tachycardia, despite the addition of adrenaline to the LIA mixture. No difference in mortality was found between the two groups (P=0.11). CONCLUSION: These results show safe use of high volume ropivacaine with adrenaline as local infiltration analgesia during total knee replacement surgery.

Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy.

In a retrospective study, we determined clinical and serological findings, associated tumours, outcome and prognostic factors in 73 Hu-Ab positive patients detected in a Dutch reference laboratory. The most frequent signs and symptoms at presentation were sensory neuropathy (55 %), cerebellar degeneration (22 %), limbic encephalitis (15 %) and brainstem encephalitis (16 %). 23 % developed autonomic dysfunction including gastro-intestinal motility disorders in 14 %. In 85 % a tumour was detected, which was a lung tumour in 77 %. Signs, symptoms and associated tumours did not differ in six patients with additional neuronal antibodies (anti-amphiphysine, anti-CV2, anti-Ri). The overall 3 months, one-year and three-year survival rates from the time of diagnosis were 64 %, 40 % and 22 %. Rankin Scale Score (RS) at diagnosis and presence of tumour at the time of diagnosis predicted mortality with hazard ratios (95 % CI) of 2.6 (1.5-4.6) and 1.5 (1.1-2). The median delay between onset of symptoms and Hu-Ab diagnosis was 4 months. There was a negative association between delay RS at diagnosis (P=0.03). In a logistic regression analysis, only older age (OR=0.15; 0.02-0.63) and a higher RS at diagnosis (OR=0.29; 0.11-0.73) were associated with a lower probability of successful functional outcome. Adjusted for these factors, antitumour therapy showed a higher but statistically not significant probability of successful outcome (OR=3.5; 0.87-14.3). Our study underlines the importance of early diagnosis and start of antitumour treatment when the patient is still in a better functional state. The delay between onset of symptoms and diagnosis of PEM/SN suggests a window for improving outcome in these patients.

Opioid chronopharmacology: influence of timing of infusion on fentanyl's analgesic efficacy in healthy human volunteers.

Chronopharmacology studies the effect of the timing of drug administration on drug effect. Here, we measured the influence of 4 timing moments on fentanyl-induced antinociception in healthy volunteers. Eight subjects received 2.1 µg/kg intravenous fentanyl at 2 pm and 2 am, with at least 2 weeks between occasions, and 8 others at 8 am and 8 pm. Heat pain measurements using a thermode placed on the skin were taken at regular intervals for 3 hours, and verbal analog scores (VAS) were then obtained. The data were modeled with a sinusoid function using the statistical package NONMEM. The study was registered at trialregister.nl under number NTR1254. A significant circadian sinusoidal rhythm in the antinociceptive effect of fentanyl was observed. Variations were observed for peak analgesic effect, duration of effect, and the occurrence of hyperalgesia. A peak in pain relief occurred late in the afternoon (5:30 pm) and a trough in the early morning hours (5:30 am). The difference between the peak and trough in pain relief corresponds to a difference in VAS of 1.3-2 cm. Only when given at 2 am, did fentanyl cause a small but significant period of hyperalgesia following analgesia. No significant changes were observed for baseline pain, sedation, or the increase in end-tidal CO(2). The variations in fentanyl's antinociceptive behavior are well explained by a chronopharmacodynamic effect originating at the circadian clock in the hypothalamus. This may be a direct effect through shared pathways of the circadian and opioid systems or an indirect effect via diurnal variations in hormones or endogenous opioid peptides that rhythmically change the pain response and/or analgesic response to fentanyl.

Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients.

Paraneoplastic cerebellar degeneration (PCD) is a heterogeneous group of disorders characterized by subacute cerebellar ataxia, specific tumour types and (often) associated antineuronal antibodies. Nine specific antineuronal antibodies are associated with PCD. We examined the relative frequency of the antineuronal antibodies associated with PCD and compared the neurological symptoms and signs, associated tumours, disability and survival between groups of PCD with different antibodies. Also, we attempted to identify patient-, tumour- and treatment-related characteristics associated with functional outcome and survival. In a 12-year period, we examined >5000 samples for the presence of antineuronal antibodies. A total of 137 patients were identified with a paraneoplastic neurological syndrome and high titre (> or =400) antineuronal antibodies. Fifty (36%) of these patients had antibody-associated PCD, including 19 anti-Yo, 16 anti-Hu, seven anti-Tr, six anti-Ri and two anti-mGluR1. Because of the low number, the anti-mGluR1 patients were excluded from the statistical analysis. While 100% of patients with anti-Yo, anti-Tr and anti-mGluR1 antibodies suffered PCD, 86% of anti-Ri and only 18% of anti-Hu patients had PCD. All patients presented with subacute cerebellar ataxia progressive over weeks to months and stabilized within 6 months. The majority of patients in all antibody groups had both truncal and appendicular ataxia. The frequency of nystagmus and dysarthria was lower in anti-Ri patients (33 and 0%). Later in the course of the disease, involvement of non-cerebellar structures occurred most frequently in anti-Hu patients (94%). In 42 patients (84%), a tumour was detected. The most commonly associated tumours were gynaecological and breast cancer (anti-Yo and anti-Ri), lung cancer (anti-Hu) and Hodgkin's lymphoma (anti-Tr and anti-mGluR1). In one anti-Hu patient, a suspect lung lesion on CT scan disappeared while the PCD evolved. Seven patients improved by at least 1 point on the Rankin scale, while 16 remained stable and 27 deteriorated. All seven patients that improved received antitumour treatment for their underlying cancer, resulting in complete remission. The functional outcome was best in the anti-Ri patients, with three out of six improving neurologically and five were able to walk at the time of last follow-up or death. Only four out of 19 anti-Yo and four out of 16 anti-Hu patients remained ambulatory. Also, survival from time of diagnosis was significantly worse in the anti-Yo (median 13 months) and anti-Hu (median 7 months) patients compared with anti-Tr (median >113 months) and anti-Ri (median >69 months). Patients receiving antitumour treatment (with or without immunosuppressive therapy) lived significantly longer [hazard ratio (HR) 0.3; 95% confidence interval (CI) 0.1-0.6; P = 0.004]. Patients > or =60 years old lived somewhat shorter from time of diagnosis, although statistically not significant (HR 2.9; CI 1.0-8.5; P = 0.06).