Ultrasound-guided femoral approach for coronary angiography and interventions in the porcine model.

Coronary angiography and percutaneous coronary intervention (PCI) procedural details in swine are similar to those performed to humans, since their heart and coronary anatomy closely resembles. However, only a few detailed descriptions of the procedure are available, containing notable differences. We present a feasible and reproducible protocol for percutaneous coronary interventions in porcine experimental models, utilizing ultrasound-guided femoral approach. Nine female pigs were studied to explore the feasibility of superficial femoral arterial (SFA) access for coronary angiography and provisional PCI, as well as the most suitable guiding coronary catheters and angiographic projections for the above interventions. Experiments were performed under general anesthesia, using ultrasound-guided puncture of the SFA to gain arterial access. The Amplatzer AR1® catheter, and the Right Coronary Bypass® catheter were used for the selective engagement of the right and the left coronary artery, respectively. Successful arterial access and subsequent cardiac catheterization were performed in all pigs. Only one animal required a second puncture for femoral artery access. None of the 9 animals presented any significant tachycardia or hypotensive episode. One animal developed an access site-related complication following the first catheterization procedure. During follow-up, 100% success of SFA catheterization was achieved using the same ultrasound-guided technique. The ultrasound-guided superficial femoral artery access for coronary angiography and provisional interventions in porcine models is a quick and safe alternative to the carotid artery approach. The RCB and AR1 catheters may be the best choice for the quick and easy selective coronary engagement of the right and left ostia, respectively.

Effects of pneumoperitoneum and LPS-induced endotoxemia on cerebral perfusion pressure in pigs.

Multitrauma patients commonly develop abdominal compartment syndrome, which is defined as the end result of sustained, uncorrected, intra-abdominal hypertension. We aimed to assess the effects of increased intra-abdominal pressure (IAP) upon intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in the presence or absence of lipopolysacharide (LPS)-induced endotoxemia using an experimental porcine model of pneumoperitoneum. Experimental procedures were approved by the Animal Care Review Committee of the National Veterinary Institute. Sixteen female pigs weighing 20 to 25 kg, aged 3 to 4 months were used. The animal model of increased IAP employed in our studies was produced with intraperitoneal administration of helium at 25 mm Hg under general anesthesia. After induction of pneumoperitoneum, 16 animals were randomly divided into 2 groups of 8 pigs each. One group received LPS intravenously (endotoxin group) and the second group received saline (control group). ICP, CPP, and hemodynamic variables were continuously monitored and recorded. A significant reduction of the cardiac output and concurrent increases in systemic vascular resistance and central venous pressure were observed in both groups after induction of pneumoperitoneum. ICP increased whereas CPP decreased significantly compared with baseline values in both groups after elevation of IAP. After LPS administration (endotoxin group), the cardiac output and mean arterial pressure decreased significantly. The CPP decreased further in the endotoxin group after LPS administration, whereas ICP remained unchanged. IAP increases produce significant increases in the ICP and decreases in the CPP in this animal model. LPS-induced endotoxemia further decreased CPP.

The epidemiology of cancer pain.

We identified 28 epidemiological surveys by applying a sensitive search in Medline and CancerLit databases, supplemented by hand searches. Only two surveys enrolled more than 10,000 patients with cancer. The remaining were hospital or clinic-based surveys of at most a few hundred patients. Fourteen surveys were conducted in the United States. The majority of the remaining studies were conducted in Europe (Finland, France, Germany, UK/Ireland). No single survey identified a prevalence of any type of pain below 14%. The prevalence of pain reported in these surveys varies with the specific type of pain (e.g., breakthrough pain) and/or population studied. Based on these surveys an aggregate statement could not be deduced regarding the correlation between the occurrence of pain and patient factors, disease characteristics, the setting in which care is provided (e.g., primary care or specialized oncology or pain treatment clinics), or specific treatments directed towards the underlying disease and its associated pain. However, these surveys suggest that a significant number of patients with cancer worldwide will, during the course of their disease, experience pain that requires medical and/or other treatment.

Evidence report on the treatment of pain in cancer patients.

Pain associated with cancer is of widespread concern. We conducted a systematic review to evaluate the best available evidence on the efficacy of treatments of cancer-related pain. The sources used were MEDLINE, CancerLit, and the Cochrane Library from 1966 through April 2001, as well as bibliographies of meta-analyses and review articles. We selected randomized controlled trials (RCTs) reporting on cancer pain treatment. We recorded the study characteristics, patient and disease characteristics, treatment comparisons, outcome measures, and results. The methodological quality, applicability, and magnitude of treatment effect for each study were graded. We screened 24 822 titles and selected 213 RCTs to address specific questions. RCTs of cancer pain control often enroll few subjects, have low methodological quality, offer little detail about pain characteristics and mechanisms, and involve heterogeneous interventions and outcomes. Nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, selected adjuvant medications, bisphosphonates, radionuclides, external radiation, palliative chemotherapy, and neurolytic celiac plexus block are each efficacious in relieving cancer pain. However, the retrieved RCTs indicate no difference in the analgesic efficacies of NSAIDs versus other NSAIDs, NSAIDs plus opioids versus NSAIDs alone, or NSAIDs versus opioids. Studies of adjuvant medications and behavioral therapies are too few and varied to synthesize. RCTs of the analgesic effects of corticosteroids were not retrieved in our review, although we did conduct supplemental evidence reviews concerning pain control in oral mucositis, acute herpes zoster, or postherpetic neuralgia. RCTs confirm the efficacy of diverse interventions in relieving cancer pain. The optimal initial and subsequent sequence of choices among analgesic drug types cannot be inferred from the retrieved RCTs. Patient preferences, the relative efficacy of different routes of drug administration, the side effects of analgesics, and the relation of pain control to quality of life have not been studied comprehensively. The quantity and quality of scientific evidence on cancer pain relief compare unfavorably with evidence related to treatment of other high-impact conditions, including cancer itself. One contributor to this gap is the heterogeneity of outcomes instruments employed: of 218 retrieved trials, there were 125 distinct pain outcomes assessed. In the current era of patient-centered care, improving the quality and combinability of trials on cancer pain relief should be a high research priority.

Hyperalgesia in outpatients with dermal injury: quantitative sensory testing versus a novel simple technique.

OBJECTIVE: Dermal inflammation from many causes may produce a reversible period of hyperalgesia (increased sensitivity to pain perception) or allodynia (pain from innocuous stimuli). Hyperalgesia and allodynia have received relatively little attention in clinical trials of acute pain. We sought to quantitate tactile allodynia and thermal hyperalgesia in outpatients presenting with acute dermal injuries. DESIGN: We performed a randomized clinical trial to compare standard methodology for the assessment of hyperalgesia with two novel simple quantitative techniques. PATIENTS: After Institutional Review Board approval, 40 patients presenting with acute chemical, thermal, mechanical, or infectious skin injury were subjected to a series of tests at the site of injury, an intact mirror site, and a noninjured ipsilateral control site. OUTCOME MEASURES: Quantitative thermal sensory testing (Medoc sensory analyzer) was followed by a 5-second application, in random order, of copper rods preheated in water to 40 degrees C, 43 degrees C, 46 degrees C, and 49 degrees C. Pressure testing was conducted with a 1.25-inch diameter commercially available pressure transducer gauge. RESULTS: The observed pattern of responses was remarkably consistent among testing methods. All challenges with the four different temperatures elicited pain scores on a visual analog scale markedly greater at the injured than at the mirror or control site (P < 0.001 vs control). Pressure discomfort thresholds followed a similar pattern. CONCLUSIONS: We conclude that hyperalgesia is a prominent contributor to discomfort in acute dermal injury and hence is a legitimate therapeutic target. Quantitation of the contribution of thermal hyperalgesia and tactile allodynia and assessment of their management is feasible using simple, rugged, low-cost methods. This inexpensive methodology may be useful in everyday clinical practice as well as in clinical research evaluating pharmacological agents to manage hyperalgesia.

Nonsteroidal anti-inflammatory drugs, alone or combined with opioids, for cancer pain: a systematic review.

PURPOSE: To assess the safety and efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), alone or combined with opioids, for the treatment of cancer pain. PATIENTS AND METHODS: Forty-two trials involving 3,084 patients met inclusion criteria: eight compared NSAID with placebo; 13 compared one NSAID with another; 23 compared NSAID with opioid, NSAID or opioid versus NSAID plus opioid combinations, or NSAID plus opioid combinations versus NSAID plus opioid combinations; and nine studies assessed the effect of increasing NSAID dose. RESULTS: Sixteen studies lasted 1 week or longer and 11 evaluated a single dose. Seven of eight trials demonstrated superior efficacy of single doses of NSAID compared with placebo. Only four of 13 studies reported increased efficacy of one NSAID compared with another; four other studies found that one NSAID had fewer side effects than one or more others. Thirteen of 14 studies found no difference, or minimal clinical difference, when comparing an NSAID plus opioid combination versus either drug alone. Comparisons between various NSAID plus opioid combinations were inconclusive. Four studies demonstrated increased efficacy with increased NSAID dose, without dose-dependent increases in side effects. CONCLUSION: Heterogeneity of study methods and outcomes precluded meta-analyses. Short duration of studies undermines generalization of findings on efficacy and safety. On the basis of limited data, NSAIDs appear to be more effective than placebo for cancer pain; clear evidence to support superior safety or efficacy of one NSAID compared with another is lacking; and trials of combinations of an NSAID with an opioid have disclosed either no significant difference, or at most a slight but statistically significant advantage, compared with either single entity.

Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study.

Few placebo-controlled trials have investigated the treatment of breakthrough pain (BTP) in patients with chronic pain. We evaluated the efficacy and safety of intranasal ketamine for BTP in a randomized, double-blind, placebo-controlled, crossover trial. Twenty patients with chronic pain and at least two spontaneous BTP episodes daily self-administered up to five doses of intranasal ketamine or placebo at the onset of a spontaneous BTP episode (pain intensity > or =5 on a 0-10 scale). Two BTP episodes at least 48 h apart were treated with either ketamine or placebo. Patients reported significantly lower BTP intensity following intranasal ketamine than after placebo (P < 0.0001) with pain relief within 10 min of dosing and lasting for up to 60 min. No patient in the ketamine group required his/her usual rescue medication to treat the BTP episode, while seven out of 20 (35%) patients in placebo group did (P = 0.0135). Intranasal ketamine was well tolerated with no serious adverse events. After ketamine administration, four patients reported a transient change in taste, one patient reported rhinorrhea, one patient reported nasal passage irritation, and two patients experienced transient elevation in blood pressure. A side effect questionnaire administered 60 min and 24 h after drug or placebo administration elicited no reports of auditory or visual hallucinations. These data suggest that intranasal administration of ketamine provides rapid, safe and effective relief for BTP.

Preoperative interscalene block for elective shoulder surgery: loss of benefit over early postoperative block after patient discharge to home.

UNLABELLED: We performed a randomized, prospective, parallel-group, open-label, multicenter trial to compare the effects of pre- versus postoperative interscalene block using levobupivacaine on postoperative pain and analgesic requirements. One-hundred-two outpatients scheduled for elective shoulder surgery were randomized to receive 30 mL of 0.5% levobupivacaine either preoperatively (PRE group) or postoperatively (POST group). Analgesic outcome measures during the postoperative period were: (a). time to first request for analgesic medication after surgery, (b). pain intensity using the visual analog scale at rest and during arm movement, and (c). total analgesic consumption of nonsteroidal antiinflammatory drugs and opioids. The time to first analgesic request did not differ between treatment groups. However, mean maximum pain intensity scores during the day of surgery were significantly less for the PRE group than the POST group, both at rest (P = 0.001) and after movement (P = 0.004). The mean opioid administered during surgery was lower in the PRE than the POST group (P < 0.001). Levobupivacaine was well tolerated in both treatment groups, and no adverse reactions were related to this local anesthetic. In conclusion, preoperative interscalene block with levobupivacaine provided superior pain control for the first 12 h after surgery, but this benefit was not maintained during the week after discharge because the subjects assumed control of their own pain relief as outpatients. IMPLICATIONS: Preoperative interscalene block with levobupivacaine provides safe and effective analgesia for same-day elective shoulder surgery, but the benefit of this one-time intervention does not persist.

A rural, community-based program can train surgical residents in advanced laparoscopy.

BACKGROUND: Advanced laparoscopy requires mastery of complex surgical skills. A steep learning curve, lack of an adequate number of cases, and a shortage of experienced staff are reasons cited as barriers to the acquisition of these skills by surgical residents. We hypothesize that advanced laparoscopy can be taught during residency without additional fellowship training. STUDY DESIGN: ast surgical residents who completed training at our rural, community-based, 140-bed hospital from 1992 to 2000 were contacted by mailed surveys and a followup telephone interview. Advanced laparoscopy was defined as cases other than cholecystectomy, appendectomy, and diagnostic laparoscopy. Five attending surgeons routinely perform advanced laparoscopy. RESULTS: The response rate to the survey was 93.3% with 15 of 18 graduates currently practicing general surgery and 100% of the surgeons performing advanced laparoscopy. Laparoscopic herniorrhaphy, splenectomy, colectomy, Nissen fundoplication, and adrenalectomy were performed by 12 (85.7%), 10 (71.4%), 11 (78.6%), 13 (92.9%), and 9 (64.3%) surgeons, respectively. Eight (57.1%) surgeons reported confidence to perform advanced laparoscopy immediately after residency. All graduating chief residents from the last 3 years expressed this confidence. On average each of two chief residents from the past 3 academic years graduated with 99 basic and 50 advanced laparoscopic cases. CONCLUSIONS: A rural, community-based program can train residents to perform advanced laparoscopy. Increasing the volume of advanced cases handled by resident correlates with increasing confidence in graduates.

Effects of statins on nonlipid serum markers associated with cardiovascular disease: a systematic review.

BACKGROUND: Statins reduce cardiovascular events to a greater extent than can be explained by their effect on lipids. Several studies have attempted to elucidate mechanisms by which statins reduce cardiovascular risk. PURPOSE: To summarize the effects of statins on nonlipid serum markers and to correlate statins' effect on serum markers with lipid levels and cardiovascular outcomes. DATA SOURCES: MEDLINE (1980 to 2003) search limited to English-language articles. STUDY SELECTION: Studies reporting original data in at least 10 participants on the effect of statins on outcomes of interest, excluding studies of cerivastatin, drug combinations, and patients with organ transplants. DATA EXTRACTION: Study design, sample size, treatment, and outcome data extracted on the basis of preestablished criteria. When appropriate, meta-analysis was performed by using a random-effects model. DATA SYNTHESIS: All statins are effective at lowering C-reactive protein levels, and the effect is not dose-dependent. Studies do not demonstrate a correlation between statins' effects on C-reactive protein levels and on lipids or cardiovascular outcomes. Statins do not affect fibrinogen levels, and limited data suggest little effect on lipid oxidation, tissue plasminogen activator, or plasminogen activator inhibitor. Platelet aggregation data are inconclusive. CONCLUSIONS: Among nonlipid serum markers examined, only C-reactive protein levels are statistically significantly affected by statins. These findings suggest that statin-mediated anti-inflammatory effects may contribute to the ability of statins to reduce risk for cardiovascular disease. Overall, however, available data are insufficient to support recommendations for using nonlipid serum markers in decisions regarding statin therapy for individual patients.

Antihyperalgesic effect of simultaneously released hydromorphone and bupivacaine from polymer fibers in the rat chronic constriction injury model.

We aimed to evaluate the antihyperalgesic efficacy of a combination of hydromorphone (HM) and bupivacaine (BP) delivered via controlled release from a biodegradable cylindrical rod. In vivo studies were performed using a rat model of thermal hyperalgesia induced by chronic constriction injury (CCI) of the sciatic nerve with loose ligatures. Poly(lactic-co-glycolic acid) (PLGA) rods (10 mm length, 1 mm diameter) loaded with HM (5 mg per rod), BP (5 mg per rod) or no drug (placebo) were implanted subcutaneously, in single or dual pairs, adjacent to the constriction injury, immediately after nerve ligation. We evaluated the efficacy of two dose levels for each drug, alone or in combination, in attenuating thermal hyperesthesia over a period of 12 days according to a prevention protocol. Plasma levels of drugs released from the rods and also released in an in vitro simulation were evaluated. In vitro studies demonstrated that drug release is maintained for at least 10 days. HM (5 mg) alone and BP (5 mg) alone did not attenuate hyperalgesia. Their combination provided a significant increase in the paw withdrawal latency as compared to single agents or placebo. When the dose in each group was doubled, implanting four rods, significant attenuation of hyperalgesia was observed. Analyses of rods retrieved after termination of experiments (after 12 days) revealed 30% residual HM and 70% residual BP content. Prolonged delivery of HM and BP alone or in combination via locally applied PLGA rods may offer a feasible alternative to provide long-lasting analgesia.