[New views on the physiology of wound healing]. / Novi aspekti fiziologije zarastanja rana.

INTRODUCTION: A great deal of progress has been made in the last few decades in understanding the cellular and biochemical interplay that comprises the normal wound healing response. This response is a complex process involving intricate interactions among a variety of different cell types, structural proteins, growth factors and proteinases. PHASES OF WOUND HEALING: Acute wounds maturate through phases of coagulation, inflammation, matrix synthesis and deposition, angiogenesis, fibroplasia, epithelialization, contraction and remodelling, but three classic phases of wound healing are inflammation, fibroplasia and maturation. DERMAL FIBROPROLIFERATIVE DISORDERS: Two main forms of fibroproliferative disorders are hypertrophic scars and keloids. These disorders are characterized by an overabundance of wound collagen through overproduction of collagen or impaired degradation of collagen. Hypertrophic scars are raised, pruritic and edematous lesions that do not exceed the margins of the original wound (in contrast to keloids). Histologically, these lesions are indistinguishable and are characterized by thick, hyalinized collagen bundles arranged in nodules. The degree of hypertrophic scarring is believed to be related to the duration of time during which the wound is allowed to remain in inflammatory phase of healing. Wound closure tension may also play a role by altering the intracellular cytoskeletion of fibroblasts and increased secretion of TGF-beta and cytokines. CONCLUSION: Healing of chronic cutaneous wounds is still a great problem of modern society--huge costs, impaired quality of life. In the last few decades a great progress was made in understanding the cellular and biochemical interplay.

Intensive-care management of a patient with HELLP syndrome--case report.

HELLP syndrome belongs to the group of pathological states known as pregnancy-induced hypertension or EPH gestosis. The basic criteria for establishing the diagnosis are as follows: H for hemolysis, EL for elevated liver enzymes and LP for low platelets. A pregnant woman, 38 years of age, multipara (V pregnancy, third delivery) has been admitted to the Clinic of Gynecology and Obstetrics in Novi Sad in 36-37 week gestation complaining of nausea, vomiting, epigastric pain, general weakness, exhaustion as well as symptom of previously diagnosed preeclampsia. Due to signs of fetal distress, the patient has undergone urgent cesarean section, giving birth to a female premature newborn infant. Twenty-four hours after delivery all symptoms and signs HELLP syndrome manifested. Being in a critical state, the patient has been transferred to the Institute of Surgery, Clinic of Anesthesiology and Intensive Care with signs of multiple organ failure. With this case report of a patient with HELLP syndrome, we wished to point to importance of continual intensive clinical follow-up, laboratory monitoring and corresponding therapeutic procedures, and at the same time to this relatively rare syndrome.

[Preemptive analgesia in cholecystectomy using pethidine]. / Preemptivna analgezija petidinom u holecistektomiranih pacijenata.

INTRODUCTION: Preemptive analgesia given before noxious stimulation prevents or reduces subsequent pain. Pain associated with central sensitization is called pathological pain. Preemptive analgesia could be defined as analgesia that prevents the development of pathological pain. The clinical significance of central sensitization lies in prediction that preemptive analgesia may prevent the establishment of central sensitization and reduce pain experienced following peripheral injury. Various pharmacological agents and methods have a potential in prevention of acute postoperative pain by blocking the somatosensory system and abolishing hypersensitivity. But the role of preemptive analgesia in postoperative pain is still controversial. The goal of the present study was to examine whether pethidine administration before skin incision is more effective in reducing postoperative pain than the same dose of pethidine given intraoperatively. MATERIAL AND METHODS: Thirty patients (ASA 1 to 2), aged from 40 to 65 years, admitted for elective laparotomic cholecystectomy entered the study. Group 1 (n = 15) received 1 mg/kg of pethidine i.v. 5 minutes before induction of anaesthesia (before skin incision) and 0.9% NaCl of equal volume intraoperatively (after peritoneal opening). Group 2 (n = 15) received pethidine and 0.9% NaCl in a reverse manner. Premedication was omitted. No other analgesics were administered at induction and intraoperatively. Anaesthesia was induced with midazolam, thiopentone and succinylcholine for tracheal intubation. Pancuronium was administered for muscle relaxation and halothane with O2/N2O for maintenance of anaesthesia. The duration of surgery (time from skin incision to skin closure) and time from skin closure to the first analgesic request were measured and recorded. In the ward, patients were given metamizol (2500 mg) i.m. at request during the first 12 h. If the regimen was not sufficient, piritramide (2 mg) i.m. was given at request. The intensity of pain was estimated before the first analgesic request and 4, 8, 12 and 24 h thereafter. Pain scores were recorded using VAS (0 = no pain; 10 = worst pain). Data are presented as mean values with their standard deviations and as the ranges of each parameter. The differences in data between two groups were evaluated with Student's t-test. P > 0.05 was considered statistically significant. RESULTS: Demographic data, duration of surgery and time from skin closure to the first analgesic request are presented in Table 1. No significant difference was found between the two groups. The postoperative analgesic requirements in two groups were similar and piritramide requirement was omitted. VAS scores at each time (Table 2) did not differ between the two groups. DISCUSSION: The findings of many clinical investigations remain controversial. Some clinical studies comparing the same analgesic intervention before and after the painful stimulus have shown a benefit of preemptive analgesia. The results of our study did not show a significant difference in pain scores neither in analgesic requirements of patients who received systemic pethidine before the painful stimulus compared with the patients treated with the opioid intraoperatively. However, epidural opioid administration may be more effective (17,18). It is important to say that inhalational anaesthetics, including N2O and some i.v. anaesthetic agents may have preemptive effects themselves, significantly reducing spinal sensitization (19,20). In clinical studies when the preemptive effect of analgesics is under investigation, inhalational and i.v. anaesthetics which are administered to induce and maintain anaesthesia are given before surgery. Therefore development of central sensitization may be attenuated or prevented by the anaesthetics overlapping the preemptive effect of analgesics. CONCLUSION: The results of this study did not demonstrate a preemptive effect of pethidine. (ABSTRACT TRUNCATED)

[Sedation and analgesia in intensive therapy]. / Sedacija i analgezija u intenzivnoj terapiji.

INTRODUCTION: In the operating room, anaesthetist must provide unconsciousness, analgesia and muscular relaxation. In intensive therapy (IT), the rules are different and not every patient requires sedation, but almost every patient needs analgesia. The patient who is alert, calm and comfortable despite the presence of tubes and cannulas in the nose, mouth, radial artery, central vein, urethra, surgical wounds, pleural space etc. does not need any sedation. However, sedation and analgesia are clinically inseparable. If mechanical ventilation is not well controlled, muscular relaxants must be prescribed. There are a lot of trials in formulating an ideal sedative/analgesic regimen for each individual patient. THE RISKS OF SEDATION AND ANALGESICS: It is not rare that IT patients are oversedated or undersedated. Undersedation is followed by anxiety, pain, hypertension, tachycardia. The most important effect of oversedation is respiratory depression, hypotension, bradycardia, CNS depression, renal dysfunction, immunological depression. SEDATIVES AND HYPNOTICS: Benzodiazepines are among the most widely used drugs in IT. They have sedative, hypnotic, anxyolytic, amnestic, anticonvulsant and myorelaxant effects. Prolonged continuous infusion of benzodiazepines ought to be escaped because of prolonged sedation, accumulation and presence of pharmacologically active metabolites. They have proved to be safe, although they can depress ventilation. Since benzodiazepines are not analgesics, the combined use of an opioid and benzodiazepines is necessary. Many different benzodiazepines are available, but the agents most commonly used in critically ill are: midazolam, diazepam and lorazepam. Midazolam is the most extensively used. PSYCHOTROPIC DRUGS: The most frequently used drugs in the group of the butyrophenones are droperidol and haloperidol. Although these drugs are chemically unrelated to the phenothiazines they have similar actions. ANALGESICS: Opioids have the main place in management of analgesia in IT, especially in patients on mechanical ventilation. In management of postoperative analgesia, epidural route has advantage because less drug is necessary and cardiovascular and respiratory effects are minimal. Morphine is a standard opioid to which all others are compared. Intravenous bolus dose is 1-5 mg (0.1-0.15 mg/kg) or continuous infusion 2-15 mg/h. Hypotensive effect is caused by direct vasodilation and relief of histamine. Morphine has long elimination half-time and there is a danger of acummulation after prolonged administration. Morphine metabolites are pharmacologically active and renally eliminated. Prolonged i.v. infusion needs careful titration because of tolerance. Pethidine is less potent than morphine, usually given as a bolus dose (10 mg) or a continuous i.v. infusion (10-20 mg/h). Other opioid agents used in IT are: fentanil, alfentanil, sufentanil. Non-steroidal anti-inflammatory drugs (NSAID-s) are: aspirin, ibuprofen, ketoprofen, diclofenac, ketorolac. NSAID-s may have an opioid sparing effect and be of particular benefit for the relief of pain from bones and joints. They interfere with the metabolism at the site of the sensory nerve terminals. Several chemicals are released locally in response to tissue injury. Arachidonic acid is produced from damaged cell membranes. One series reactions is mediated by the enzyme cyclo-oxygenase (COX) and results in the formation of prostaglandins, prostacyclins and thromboxane. The cyclo-oxygenase pathway is inhibited by NSAID-s. These analgesics, besides peripherally, also work centrally by mechanisms which are not in connection with COX inhibition. INTRAVENOUS AND INHALED ANAESTHETIC AGENTS: There are two barbiturates in use: thiopentone and pentobarbital. Although the main effect is hypnosis, the most important is anticonvulsant effect. Thiopentone is an agent for cerebral protection. Barbiturates have not achieved popularity in IT because of prolonged elimination and slow recov