Pulmonary function in the early postoperative period

To the author's knowledge, an intensive investigation of pulmonary function during the first 2 postoperative days has not previously been reported. Consequently, in this study the effect of regional surgery on respiratory function, monitored every 4 h during the first 2 postoperative days, was analyzed. Hypoxaemia was a constant finding in all patients undergoing general anaesthesia. The degree and duration of hypoxaemia and spirometry changes were related to the site of surgical incision. Clinical signs of atelectasis were commonly observed during the first postoperative day and occurred after the change in PO2 and spirometry. Atelectasis was more common in patients having upper abdominal surgery. The current investigation reveals that the earliest postoperative change indicative of atelectasis is the fall in PO2; that auscultatory changes do not always occur in the presence of postoperative hypoxaemia; that auscultatory signs are not indicative of the extent of the PO2 fall; and that radiology represents a crude method of assessing postoperative atelectasis.     

Gastrointestinal complications associated with intramuscular ketorolac tromethamine therapy in the elderly

OBJECTIVE: To report 3 cases of gastrointestinal (GI) complications associated with the use of intramuscular ketorolac tromethamine therapy in elderly patients. CASE SUMMARIES: In case 1, an 88-year-old woman was taken to surgery for the management of an acute abdomen and repair of a 2+ cm perforated prepyloric gastric ulcer. The patient had received a total 16 doses of ketorolac 30 mg im. The patient died after surgery from complications associated with bacterial and candidal sepsis, as well as acute renal failure. In case 2, an 80-year-old woman with no known history of GI problems developed a prepyloric gastric ulcer, which perforated and penetrated into the pancreas after the patient received 13 doses of ketorolac 30 mg im. The patient died from complications associated with candidal sepsis, peritonitis, and cardiopulmonary collapse. In case 3, an 85-year-old man with a history of a gastric ulcer developed GI bleeding after receiving a total of 9 doses of ketorolac 30 mg im. The bleeding was stabilized and the patient was discharged 12 days later in stable condition. DISCUSSION: Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug with potent analgesic properties. We report 3 cases of GI complications associated with intramuscular ketorolac therapy in the elderly. A temporal relationship was established with the development of gastric ulceration in 2 patients and the recurrence of a gastric ulcer in the third patient. CONCLUSIONS: We recommend that the manufacturer's guidelines be followed when ketorolac is used in elderly patients, and the drug should not be used in patients with a history of gastric ulcer disease. The use of misoprostol may be warranted as prophylactic therapy in high-risk patients who are receiving ketorolac.     

Ozone therapy of diffuse peritonitis in the early postoperative period

The functional status of the oxidative-antioxidative system was studied in 72 patients after vast cancer operations. Traditional surgical treatment and its combination with intraoperative irradiation were shown to lead to tense antioxidative defense and to suppressed T-cell immunity and to call for antioxidative and immunomodulating therapy. High intraoperative blood loss complicated by hemorrhagic shock injured the oxidative-antioxidative system greatly. The magnitude of this damage correlated with the rate of prehypoxia. Addition of the potent antioxidant Ceruloplasmin to the drug regimen normalized a recovery period, helped to correct posthypoxic multiorgan insufficiency, to recover oxidative-antioxidative balance, and to decrease the incidence of pyoinflammatory complications. Patients with endogenous intoxication showed activated lipid peroxidation, decreased functional activity of antioxidative defense components and of T-cell immunity in homeostasis. The use of Ceruloplasmin and Laprot had pronounced antiinflammatory and detoxifying effects on the patient's body and activated its antioxidative defense.     

The use of Diprivan as an anticonvulsant in the early postoperative period of an otogenic brain abscess

This is a report on a female patient with otogenic cerebellar abscess and symptomatic generalized convulsions, irresponsive to conventional diazepam and phenobarbital therapy. Fractionated propofol administration yields good effect without noteworthy changes in respiration and circulation.     

Postoperative ileus as an indication for a 2d operation during the early postoperative period

The phagocytic and bactericidal activities to Salmonella pullorum (strain 9-25) or Salmonella senftenberg (strain 99D) were examined in chicken splenic phagocytes from 0-day-old to 2-month-old chickens. The phagocytic activity against S pullorum increased in splenic phagocytes from chickens older than 7 days, but significant changes in activity against S senftenberg were not observed during the experimental period. The bactericidal activity of splenic phagocytes against S senftenberg was higher than that of phagocytes against S pullorum during the same period. Increase of the bactericidal activity against S pullorum was observed with increasing age, but the activity of the splenic phagocytes from 0-day-old chickens against S senftenberg was similar to that of the phagocytes from 2-month-old chickens. Although delayed hypersensitivity was confirmed by delayed wattle reaction in 2-month-old chickens sensitized with living S pullorum, the sensitization did not markedly affect phagocytic and bactericidal activities.     

Gastrointestinal myoelectrical activity during the postoperative period in man

Myoelectrical activity of the gastrointestinal tract has been studied in the postoperative period of 13 patients who underwent cholecystectomy. The recordings have been performed by means of extracellular electrodes which were implanted at the levels of stomach, jejunum, ileum and colon during the surgical procedure. The records showed that fast activity is always persistent while the basic electrical rhythm is greatly disorganized during the immediate postoperative period. Such a characteristic pattern of the electrical activity suggested that the lack of peristaltic and propulsive movements, always noted during this period, is not correlated with a disappearance of gastrointestinal contractions, but only with a disturbance in their coordination.     

Medication use during the perinatal period

OBJECTIVE: To briefly describe the drug therapy administered during the perinatal period of pregnancy for common maternal and fetal complications, and to identify those agents that should not be used for these conditions. DATA SOURCES: References were obtained from an ongoing literature search of peer-reviewed obstetric and gynecologic journals and other selected medical and pharmacy journals available in the English language. Primary search vehicle was a weekly review of the tables of contents of nearly 1,300 medical journals provided by Reference Update (Institute of Scientific Information, Philadelphia). MEDLINE searches were also conducted using key terms for each subtopic. STUDY SELECTION: Specific references were selected for each topic based on the adequacy of their study design, patient population, and a recent publication date. Reviews were used if a large number of primary references would have been required to adequately describe the topic. DATA EXTRACTION: Most references reflected the current opinions expressed in the Educational (Technical) Bulletin and Committee Opinion series published by the American College of Obstetricians and Gynecologists. Recent, well-conducted studies that arrived at different conclusions were also included. DATA SYNTHESIS: Data obtained from each reference reflected the conclusions of the authors based on their research or an analysis of the research on others on the appropriate use of the drug(s) for the specific condition being treated. CONCLUSION: Drug therapy during the perinatal period is frequently required and can be beneficial for the mother, fetus, and newborn. Many complications previously associated with severe morbidity and mortality, such as infections, premature rupture of membranes, preterm labor, hypertension, maternal pain during labor, and postpartum hemorrhage, are now controlled with appropriate pharmacologic therapy. All health professionals who provide services to pregnant women should be knowledgeable in this drug therapy.     

Does the preoperative administration of ketorolac improve postoperative analgesia

AIM OF THE STUDY: 1) To verify the usefulness of ketorolac administration (30 mg i.v.) before a surgical operation in terms of postoperative analgesia improvement; 2) To evaluate the impact of preoperative ketorolac administration on perioperative renal function and on intraoperative water balance; 3) to evaluate the presence of adverse effect due to preoperative NSAID use. DESIGN: Prospective randomized trial. SETTING: University surgical department. PATIENTS AND METHODS: Forty adult patients undergoing major abdominal surgery, randomized in 2 groups: in group 1 ketorolac (30 mg i.v.) was administered immediately after the induction and, for postoperative analgesia, ketorolac (30 mg i.v.) was administered beginning at the time of skin closure; in group 2 no ketorolac was administered before the operation and postoperative treatment was the same. Buprenorphine (0.3 mg i.m.) was administered in case of unsatisfactory analgesia. Fluids infused and diuresis were measured intraoperatively. One, 6 and 24 hours after the end of operation pain was evaluated using pain intensity score and VAS. The day after the operation serum creatinine and urea were measured. RESULTS: No statistically significant differences were found between groups regarding fluids infused, intraoperative diuresis, postoperative pain, adverse effects and number of bleeding episodes. More than 50% of patients, in either groups, required opioids administration. CONCLUSIONS: Ketorolac (30 mg i.v.) administration before a major abdominal operation does not improve postoperative analgesia nor determines significant alterations in renal function or increase in the frequency of abnormal bleedings. Opiate administration is necessary in more than 50% of the patients to achieve adequate analgesia.     

In vitro transcorneal permeation of ketorolac tromethamine from buffered and unbuffered aqueous ocular drops

In vitro transcorneal permeation of ketorolac tromethamine from 0.5% w/v solutions containing equimolar (0.02 M) concentrations of citrate (pH 6.5), phosphate (pH 6.5 and 7), citrate-phosphate (pH 7) and borate (pH 7) buffers was studied using goat cornea. Cumulative % permeation was maximum with phosphate buffered drops of pH 6.5. The effect of pH and ionic strength on permeation of ketorolac tromethamine from buffered (phosphate) drops was next investigated. Cumulative % permeation of ketorolac tromethamine from buffered drops was pH dependent being maximum at pH 4.5. Adjustment of ionic strength of drops to 0.2 resulted in decreased permeation of drug. Permeation of ketorolac tromethamine from unbuffered drops of varying pH and ionic strength 0.2 was also pH dependent and was maximum at pH 4.5. Buffered drops of pH between 4.5-5.5, ionic strength 0.2, provided better permeation of drug compared to unbuffered drops of same pH and ionic strength. Above pH 6.5 unbuffered drops showed better permeation than buffered drops. Increase in molarity of phosphate buffer (pH 4.5) used in making drops, between 0 to 0.15 M increased permeation. Aqueous drops of ketorolac tromethamine formulated in 0.15 M phosphate buffer of pH 4.5 and ionic strength 0.2 showed maximum cumulative % permeation in vitro. Considering lacrimation induced drug loss in vivo, by buffer of high concentration, ketorolac tromethamine drops formulated in buffer of low molarity, pH 4.5 and ionic strength 0.2 appear suitable.     

The intraoperative administration of ketorolac tromethamine in evaluating length of stay in a same day surgery unit

Relative biological effectiveness (RBE), as a function of linear energy transfer (LET), is evaluated for different types of damage contributing to mammalian cell reproductive death. Survival curves are analysed assuming a linear-quadratic dose dependence of lethal lesions. The linear term represents lethal damage due to single particle tracks, the quadratic term represents lethality due to interaction of lesions from independent tracks. RBE-LET relationships of single-track lethal damage, sublethal damage, potentially lethal damage and DNA double-strand breaks (dsb) are compared. Single-track lethal damage is shown to be composed of two components: damage that remains unrepaired in an interval between irradiation and assay, characterized by a very strong dependence on LET, with RBEs up to 20, and potentially lethal damage, which is weakly dependent on LET with RBEs < 3. Potentially lethal damage and sublethal damage depend similarly on LET as DNA dsb. The identification of these different components of damage leads to an interpretation of differences in radiosensitivity and in RBEs among various types of cells.     

Comparison of ketorolac tromethamine with other injectable nonsteroidal anti-inflammatory drugs for pain-on-injection and muscle damage in the rat

The local tolerance of ketorolac tromethamine (Toradol, Syntex) was compared with that of four other injectable nonsteroidal anti-inflammatory drugs (NSAIDs) (diclofenac sodium, piroxicam, ketoprofen, and metamizol magnesium) in the rat paw-lick/muscle irritation assay as described previously. All drugs were tested at concentrations approved for clinical use. After subplantar (footpad) injection, ketorolac produced virtually no pain-on-injection as assessed by the number of paw-lick/lift responses during a 15 min observation period. The other NSAIDs produced slight to moderate paw-lick/lift responses. Redness and swelling at the injection site were less severe for ketorolac than for the other NSAIDs. After intramuscular (i.m.) injection, all of the NSAIDs produced some degree of muscle damage, as assessed histopathologically 24 h after injection. The lesions, consisting primarily of muscle degeneration, were less severe for ketorolac than for the other NSAIDs. Ketorolac and metamizol produced the smallest elevations in serum creatine kinase, as measured 2 h after i.m. dosing, not significantly different from isotonic saline. Overall, ketorolac was better tolerated in the assay than the other injectable NSAIDs, thereby suggesting the possibility of improved local tolerance on clinical use.     

Changes in plasma levels of lipid peroxidation products and myoglobin in patients with malignant tumors in the early postoperative period

Changes in the levels of free myoglobin and lipid peroxidation products (hydroperoxides and malonic dialdehyde) were studied in cancer patients. Their baseline levels were found to be higher in patients with cancer of the lung, large bowel, and rectum than those in controls, which indicates higher lipid peroxidation, which led to the destabilization of cellular membranes and seems to cause baseline hypermyoglobinemia. There was a drastic rise in the levels of free myoglobin in the first 24 postoperative hours. The duration and severity of hypermyoglobinemia were much higher in the complicated than uncomplicated postoperative period. There was a less rise in malonic dialdehyde concentrations, whose peak was observed on days 1-2 postsurgery. The content of hydroperoxides decreased in the first 24 postoperative hours and began gradually increased from day 2. The correlation between the concentrations of myoglobin and malonic dialdehyde suggests that there is an association between hypermyoglobinemia and the status of cellular membranes.     

Complete small bowel obstruction in the early postoperative period complicating surgical sling procedure

The surgical insertion of an absorbable sling mesh has become the most promising technique for excluding the small bowel from the pelvis prior to radiotherapy. Both human and animal studies suggest that this procedure is very safe. The author reports what appears to be the first significant mesh-related complication. A 69-year-old man suffered early postoperative complete mechanical small bowel obstruction after insertion of a polyglactin 910 (Vicryl) surgical sling mesh at the time of low anterior resection for a stromal sarcoma of the rectum. Urgent laparotomy was required and revealed that the Vicryl mesh was associated with an intense inflammatory reaction. Radiation therapy is a critical component of contemporary multimodal treatment of patients with rectal cancer. This case suggests that inserting biodegradeable mesh to protect the small bowel from radiation effects is not without complications.     

Transdermal delivery of ketorolac tromethamine: permeation enhancement, device design, and pharmacokinetics in healthy humans

Transdermal delivery of ketorolac tromethamine, a potent non-narcotic analgesic, through human skin in vitro and in vivo was investigated. In order to enhance and sustain the flux of ketorolac through human skin, various compositions of isopropyl alcohol (IPA), water, and isopropyl myristate (IPM) were evaluated. The solubility of ketorolac acid in an IPA/water binary vehicle mixture increased as the volume fraction of IPA increased from 0 to 90%. The solubility of ketorolac acid in an IPA/water/IPM (saturated) ternary vehicle mixture was practically the same as in the IPA/water binary vehicle mixture. The permeation of ketorolac acid through cadaver skin was evaluated using modified Franz diffusion cells. The skin flux increased as the IPA volume fraction was increased from 0 to 50% and then leveled off beyond 80% IPA loading. When IPM was added to the IPA/water binary vehicle mixture, a significant increase in the skin flux of ketorolac was observed. The skin flux decreased exponentially as the donor solution pH was raised from 3.5 to 7.0. The permeability of ketorolac through various membranes such as a microporous membrane and pressure-sensitive adhesive was evaluated. While a microporous membrane offered practically no diffusion resistance, the in vitro flux of ketorolac through cadaver skin decreased substantially upon lamination of pressure-sensitive adhesive onto a microporous membrane. Three liquid-reservoir type transdermal devices were fabricated using 6.5% ketorolac tromethamine gel, a microporous membrane, an adhesive membrane, and polyester backing film: TD-A (microporous membrane/acrylic adhesive), TD-B (microporous membrane/silicone adhesive), and TD-C (microporous membrane). The pharmacokinetics of ketorolac in 10 healthy humans following application of a transdermal device for 24 h was evaluated. The maximum plasma concentrations (Cmax) were 0.20, 0.18, and 0.82 microgram/mL for TD-A, TD-B, and TD-C, respectively. The total AUC values for the concentration-time curves were TD-C > TD-A > TD-B, and the terminal half-life ranged from 6.6 to 9.7 h.     

Evaluation of the synergism between ketorolac and morphine in the treatment of postoperative pain

BACKGROUND: The aim of the study is to determine what concentration of ketorolac and morphine administered together i.v. achieve best synergic effect between NSAID antiinflammatory and opioids analgesic properties. DESIGN: Randomized comparative study was carried out on 180 patients, ASA II-IV, undergoing major general surgery, in an University Clinic. METHODS: Postoperative pain therapy by i.v. PCA: group 1 morphine 0.75 mg.ml + ketorolac 0.75 mg.ml; group 2 morphine 0.50 mg.ml + ketorolac 1.50 mg.ml; group 3 morphine 0.25 mg.ml + ketorolac 1.50 mg.ml; in saline solution. Initial bolus: 2 ml. Continuous infusion 1.5 ml.h. Demand bolus: 0.2 ml. Lockout time: 30 minutes. Evaluations included: pain intensity (T0, T3, T18); total amount of infused drugs (T18); number of valid demands and attempts (T18); amount of autoadministered analgesic drugs in percent of highest available amount (T18); side effects (T18); patient's judgment. DATA ANALYSIS: ANOVA and Student's "t"-test. RESULTS: A statistically significant reduction of pain intensity was found after 3 and 18 hours in the three groups, no differences were found among the groups. Group 2 required an amount of autoadministered drugs significantly lower than other groups. Rare side effects. Patient's judgment was generally positive. CONCLUSIONS: Results suggest a greater synergetic effect between morphine and ketorolac in concentrations used in group 2.