Treatment of pain in trauma patients with injuries of the upper limb.

Since preoperative pain therapy of a trauma patient did not play an outstanding role in the past, this article shall give information about the adequate treatment of such patients, which can be mainly divided into three phases: the prehospitalisation phase with stabilisation of the trauma patient, the early phase of hospitalisation with further stabilisation, diagnosis and surgery, and finally the postoperative phase with corresponding treatment. An optimal analgesic in the prehospitalisation phase should guarantee good analgesic effects, rapid onset and good controllability, simple handling and the opportunity to combine it with other medication. In addition, it should prevent a wide therapeutic range and the absence of side effects. Opioids and ketamine are available for acute pain therapy after trauma. The main opioids used are piritramide and pethidine, with piritramide acting as a sedative at the same time and with pethidine preventing the stronger analgesic effect. The intravenous use of ketamine has become established in trauma patients because of its excellent analgesia at subanaesthetic doses. Especially in multiple trauma patients, the indication for general anaesthesia with intubation should be established on a liberal basis. Nevertheless, for some patterns of injury regional techniques may be advantageous; therefore, this article describes the possible regional procedures (such as intravenous regional anaesthesia or block of peripheral nerves). Concerning the postoperative phase, an individual pain management can be guaranteed by systemic pharmacotherapy and regional catheter techniques, for example the brachial plexus blockade that results in a long period of free pain.

Continuous spinal anaesthesia or continuous epidural anaesthesia for post-operative pain control after hip replacement?

Both continuous spinal anaesthesia and continuous epidural anaesthesia are supposed to provide adequate post-operative pain relief. The purpose of this randomized, prospective study was to compare the quality of analgesia, occurrence of side effects and patient satisfaction between spinal and epidural administration of bupivacaine during the first post-operative 72 h. One hundred and two patients scheduled for hip arthroplasty were randomly assigned to one of two groups: Group 1 received continuous spinal anaesthesia for intra-operative and post-operative management, Group 2 received continuous epidural anaesthesia. Immediately after surgery, the continuous spinal anaesthesia-group received a 1-mL bolus (bupivacaine 0.25%), followed by a continuous infusion of 10 mL over 24 h. The continuous epidural anaesthesia-group received a 10-mL bolus (bupivacaine 0.25%), followed by 2 mL h-1. The level of pain was gauged from a verbal rating score and from a visual analogue scale; the degree of motor blockade was recorded using the Bromage score. In the continuous spinal anaesthesia-group 90.2% reported complete analgesia on the verbal rating scale, but only 21.6% of the continuous epidural anaesthesia-group did. The visual analogue scale scores given by the continuous spinal anaesthesia-group were significantly lower than those of the continuous epidural anaesthesia-group. The percentage of patients with a motor block was significantly higher in the continuous spinal anaesthesia-group on the day of surgery and at the first post-operative day. During the first 24 h, nausea and vomiting occurred more often in the continuous epidural anaesthesia-group. The satisfaction was considered excellent in 92.2% of the continuous spinal anaesthesia-group and in 70.6% of the continuous epidural anaesthesia-group. It is concluded that continuous spinal anaesthesia and continuous epidural anaesthesia are effective and safe for post-operative pain relief after hip replacement. Compared with continuous epidural anaesthesia, continuous spinal anaesthesia provides faster onset of pain relief, ensures better analgesia and results in more satisfied patients.

Activity of thymidine kinase and of polymerase alpha as well as activity and gene expression of deoxycytidine deaminase in leukemic blasts are correlated with clinical response in the setting of granulocyte-macrophage colony-stimulating factor-based priming before and during TAD-9 induction therapy in acute myeloid leukemia.

The present study was undertaken to assess the predictive value of pretherapeutic determinants of ara-C metabolism and proliferative activity of leukemic blasts for early response to antileukemic therapy in the setting of granulocyte-macrophage colony-stimulating factor (GM-CSF)-based priming before and during TAD-9 induction in 36 consecutive patients with de novo acute myeloid leukemia (AML). Ara-C metabolism was assessed by the activities of deoxycytidine kinase (DCK), deoxycytidine deaminase (DCD), DNA polymerase alpha (Poly alpha), and overall polymerase (overall Poly). The fraction of cells in S phase (%S phase) and thymidine kinase (TK) activity were determined as a measure of proliferative activity. Early response to therapy was defined by the percentage of leukemic blasts in the bone marrow 5 to 7 days after completion of TAD-9 with less than 5% signaling an adequate response and greater than 5% indicating an inadequate early reduction, respectively. While neither %S phase, DCK, nor overall Poly activity were predictive for early response, TK and Poly alpha activities were significantly higher for cases with adequate blast cell clearance. The respective median values were for TK 3.8 versus 1.85 pmol/min/mg protein (P = .012), and for Poly alpha 1.9 versus 0.69 pmol/min/mg protein (P = .014). An inverse relation was detected for DCD activity which was significantly lower in responding patients with a median of 0.33 nmol/min/mg protein (range, 0.0 to 29.5) as compared to a median of 5.1 nmol/min/mg protein (range, 0.11 to 8.45) in early nonresponders, (P = .009). Taking the respective median values as arbitrary cut-points for high or low enzyme activities, responders and nonresponders could be discriminated prospectively. Hence, 14 of 16 cases (88%) with DCD activities below the median of 1.56 nmol/min/mg protein responded as compared to only 3 of 14 (22%) patients with higher DCD activities (P = .0004). From the 15 patients with TK activity above the overall median of 3.2 pmol/min/mg protein, 11 cases (73%) achieved an adequate blast cell clearance while only 6 of 17 cases (35%) with lower values responded (P = .035). Similarly, 12 of 15 patients (80%) with high Poly alpha levels (>1.22 pmol/min/mg protein) responded to induction therapy as compared to only 5 of 14 patients (36%) with lower enzyme activities (P = .02). By logistic regression analysis of enzyme activities, DCD activity was found to be the most sensitive parameter to predict an adequate blast cell clearance (P = .032). Activities of DCD and TK were not only associated with initial response but were also found predictive for remission duration. Hence, from 11 patients with low TK levels 8 (73%) relapsed within 1 year, whereas only 2 of 11 (18%) patients with high TK activity experienced a recurrence of their disease (P = .015). Six of 9 (66%) patients with higher than median DCD levels relapsed within 1 year, whereas 10 of 14 patients (71%) with lower DCD levels had a longer remission duration (P = .085). Analysis of DCD gene expression at the mRNA level by a semi-quantitative reverse transcriptase-polymerase chain reaction method showed that a high transcription rate of the DCD gene was associated with high enzyme activities and vice versa. Hence, the observed intraindividual differences in DCD activity are a reflection of differences in gene activity and transcription rate rather than of variants in translation. Although further analyses are needed to elucidate the molecular mechanisms that determine the variation of enzyme activities in individual patients, the present study strongly suggests that pretherapeutic determination of TK and Poly alpha as well as of DCD allows to predict response to TAD-9 + GM-CSF induction therapy and may provide the means for the development of a risk adapted treatment strategy.

Modulation of intracellular metabolism of cytosine arabinoside in acute myeloid leukemia by granulocyte-macrophage colony-stimulating factor.

The current study investigated the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the intracellular metabolism and cytotoxicity of 1-beta-D-arabinofuranosylcytosine (araC) in leukemic cells of 45 patients with acute myeloid leukemia (AML). AML blasts from bone marrow (BM) (n = 39) and peripheral blood (PB) (n = 17) were incubated for 48 h with or without GM-CSF (100 U/ml) followed by a concurrent treatment with increasing concentrations of araC (0.06-100 microM) for an additional 24 h. After GM-CSF a 1.5-8.4-fold (median 2.3) increase in 3H-araC incorporation into the DNA was observed in ten of 14 peripheral blast specimens and in 23 of 28 bone marrow samples, 18 of whom also showed an enhanced 3H-TdR incorporation (1.5-8.5-fold, median 2.0-fold). Four different types of response were identified when analyzing 3H-araC incorporation into the DNA of bone marrow samples in relation to the applied araC dose: (i) 8/28 cases had increases of the araC incorporation at all araC dose levels applied (0.06-100 microM), (ii) 12/28 at low araC concentrations only (0.06-1.0 microM), (iii) 3/28 at high araC concentrations only (10-100 microM), and (iv) 5/28 showed no increase at any dose level given. Hence, 20 of the 23 responding patients revealed a GM-CSF induced enhancement of araC incorporation at low or conventional doses of araC (0.06-1.0 microM). Fourteen of the 18 cases with concomitant rises of 3H-TdR and 3H-araC incorporation into the DNA after GM-CSF had elevated DNA polymerase alpha activity (16-531%, median 72%) and in ten cases overall DNA polymerase activity was enhanced (10-70%, median 22.5%). In contrast, thymidine kinase (TK) and deoxycytidine kinase (dCK) activity were elevated after GM-CSF in only ten and five patients, respectively. An increase in the fraction of cells in S phase was found in 11/21 bone marrow specimens and in 5/9 peripheral blast samples. However, no correlation was observed between increases in the proportion of cells in S phase and enhancements in enzyme activities. In 13 cases the cytotoxicity of araC with and without GM-CSF was assessed by means of a blast cell colony assay. Preincubation with GM-CSF increased the araC mediated cytotoxicity in ten of 13 patients by a median of 3.2-fold (range 2.2-229-fold). The respective LD50 values for araC were reduced from 0.45 to 0.19 microM on average.(ABSTRACT TRUNCATED AT 400 WORDS)