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- Ron and Nancy McFarlane Distinguished Professor and Chair, Division of Practice Advancement and Clinical Education, UNC Eshelman School of Pharmacy, Chapel Hill, North Carolina
https://pharmacy.unc.edu/news/directory/drhoney/
In women with an unplanned pregnancy symptoms stiff neck quality 100 mg topiramate, an individualised management plan should be agreed between the woman with epilepsy and the epilepsy specialist treatment yellow jacket sting buy cheap topiramate 100 mg online. Even high-risk drugs like sodium valproate are still the drugs of choice for certain epilepsies and a discussion of risks and benefits is manda to medications ok for pregnancy order topiramate visa ry symptoms 0f high blood pressure discount topiramate 100 mg line. Other clinicians have concerns about the potential harms of increasing drug doses in pregnancy Evidence without clear evidence of benefit over risk. The findings of a systematic review on the effectiveness of the above two moni to ring methods in pregnant women taking lamotrigine were limited due to the inclusion of poor quality observational studies with small numbers of women. Given the paucity of evidence, there is no clear indication to undertake therapeutic drug moni to ring in pregnancy routinely. Clinicians will need to take in to account other features such as suspicion of non-adherence, to xicity and intractable seizures in their decisions on therapeutic drug moni to ring. Additional fac to rs such as psychosocial problems, low esteem and fear of having seizures may have a negative impact on cognitive performance. A 2015 systematic review66 identified 38 studies (2 837 325 women) examining pregnancy and reproductive outcomes in relation to epilepsy and pregnancy. There were no differences between the two groups in the odds of gestational diabetes or perinatal death. There were no significant differences between the two groups for hypertensive disorders, caesarean section, spontaneous miscarriage, antepartum haemorrhage, preterm delivery, or fetal death. There were no differences in the odds of spontaneous miscarriage, preterm delivery before 36 or 37 weeks of gestation, antepartum haemorrhage or postpartum haemorrhage. The two groups showed no difference in the odds of fetal outcomes such as small-for-gestational-age fetuses, stillbirths or admissions to the neonatal intensive care unit. Early and appropriate discussion with the epilepsy specialist nurse or neurologist is required if there is a deterioration in seizure control. Precipitants of seizures such as fasting, sleep 67 Evidence deprivation and stress should be identified and managed accordingly. Specialist advice level 4 may include altering drug doses, addition of new drugs or recommending admission to hospital. Inpatient nursing level 3 should be in an environment in which continuous care from a partner or nursing observations takes place. Fetal heart rate changes such as bradycardia and reduced variability during a seizure have been reported due to possible fetal hypoxia. Two observational level 2+ studies failed to show a beneficial effect for prenatal vitamin K to prevent haemorrhagic disease of the newborn,73,74 although it is worth noting that babies in these studies were also routinely administered 1 mg of vitamin K injection at birth. No studies have evaluated the effectiveness of antenatal administration of oral vitamin K in preventing postpartum haemorrhage. P the diagnosis of epilepsy per se is not an indication for planned caesarean section or induction of D labour. In a small proportion of women with significant deterioration of seizures, which are recurrent and prolonged, and who are at high risk of status epilepticus, elective caesarean section may be considered. Diagnostic awareness of non-epileptic attack disorder is an important first step in management. Management of women with non-epileptic attack disorder should include access to specialist psychiatric or psychological services. Close liaison is required with the neurology and mental health teams for further management where appropriate. In the absence of evidence of benefit with increased dose of steroids, and the potential harm with high steroid doses, routine doubling of steroid is not recommended. Long-acting benzodiazepines such as clobazam can be considered if there is a very high risk of seizures D in the peripartum period. If this cannot be to lerated orally, a parenteral P alternative should be administered. Adequate level 2– hydration and pain relief with an epidural will minimise the risks of seizures in labour and provides maximum safety in the event of a seizure. Avoidable delays should be minimised for planned induction of labour or elective caesarean section. The risks from clobazam, such as level 4 respira to ry depression in the newborn, need to be balanced against the benefit due to seizure prevention. P Seizures in labour should be terminated as soon as possible to avoid maternal and fetal hypoxia and D fetal acidosis. Continuous fetal moni to ring is recommended in women at high risk of a seizure in labour, and following P an intrapartum seizure. Outwith pregnancy, benzodiazepines are the drug of choice in status epilepticus: G In those with intravenous access, lorazepam given as an intravenous dose of 0. G If there is no intravenous access, diazepam 10fi20 mg rectally repeated once 15 minutes later if there is a continued risk of status epilepticus, or midazolam 10 mg as a buccal preparation are suitable. If seizures are not controlled, consider administration of pheny to in or fospheny to in. The loading dose of pheny to in is 10–15 mg/kg by intravenous infusion, with the usual dosage for Evidence an adult of about 1000 mg. After the mother is stabilised, continuous electronic fetal moni to ring should be commenced. If the fetal heart rate does not begin to recover within 5 minutes or if the seizures are recurrent, expedite delivery. Pethidine is metabolised to norpethidine, which is known to be epilep to genic when administered in high doses to patients with normal renal function. The first two are known to lower seizure threshold and the third may have epilep to genic potential. Continuous electronic fetal moni to ring is recommended in these mothers in level 4 labour. In women who are at low risk of intrapartum seizures, fetal moni to ring may be carried out by intermittent auscultation. Healthcare professionals and parents will need to be aware of the difficulties in managing a seizure in labour in this situation and the small potential risk of drowning. P Mothers should be well supported in the postnatal period to ensure that triggers of seizure deterioration such as sleep deprivation, stress and pain are minimised. P the immediate postpartum period is a high-risk period for exacerbation of seizure frequency due to increased stress, sleep deprivation, missed medication and anxiety. Sleep deprivation-related seizures could be reduced by arranging help for the mother, especially for night-time feeds. If the mother breastfeeds, s to rage of breast milk pumped during the day might be beneficial. Reviewing the daily activities of the mother and identifying high-risk situations can reduce the risks to the mother and baby due to seizures. Individualised assessment should be made for the level of post-delivery moni to ring required for withdrawal symp to ms, and for any signs of to xicity. The safety of the mother and baby in the puerperium is the most important issue to be addressed. Generalised seizures, as well as partial seizures and myoclonic jerks, can result in accidental injuries to the mother and the baby, such as drowning, falls, burns and electrocution. The discussions around caring for the baby should be initiated in the preconception period, continued antenatally and reinforced in the postnatal period. Safety strategies include nursing the baby on the floor, using very shallow baby baths, laying the baby down if there is a warning aura, not bathing the baby unaccompanied, wearing identification tags, and avoiding sleep deprivation, and alcohol if prone to myoclonic jerks. Women should ensure that family and friends have knowledge of first aid and emergency contact procedures. It is unclear whether a higher dose of levonorgestrel or ulipristal acetate is a sufficiently effective strategy. A double dose of levonorgestrel (3 mg as a single dose within 120 hours of unprotected sexual intercourse) may be used pragmatically. Although lamotrigine is not an enzyme-inducer, oral contraceptive use has been associated with a 25–70% decrease in lamotrigine trough levels, with a drop of more than 20% in the first 3 days after taking the pill. These may not take in to consideration the drug interactions which may affect ‘efficacy’ of the contraceptive, rendering it less effective. The provision of a method requires expert clinical judgement and/or referral to a specialist provider, since use of the method is not usually recommended unless other methods are not available or not acceptable.
The only way to medicine pills order topiramate 100mg on-line judge this is to medications in carry on buy topiramate with paypal see flled lungs where it has no hope of acquiring oxygen and is a time if you can detect passive chest movement in response to medicine under tongue purchase topiramate 100mg otc attempts at consuming distraction symptoms kidney problems generic topiramate 200 mg amex. If you assume that you have by the relatively large occiput of the newborn baby which will tend infated the lungs when you have not, then proceeding to chest to fex the neck. In order to open the airway of a baby the head is best compressions will not have any hope of success and you are merely held in the neutral position with the face supported parallel to surface wasting time. Over-extension of the neck is likely to when you have then you will fail to initiate chest compressions when obstruct the airway, as is fexion. The one saving Supporting the jaw and, in very foppy babies, providing formal grace is that if you actually have infated the chest then the rapidly jaw thrust is sometimes necessary. Given the relatively large size of improving chest compliance will make chest movement easier to the newborn baby’s to ngue compared to size of the mouth an oro see with subsequent imposed infations so chest movement should pharyngeal airway may also be helpful. Special case – meconium aspiration If chest movement is not seen then the airway is the problem and this Some babies who get in to difficulties before delivery may pass must be addressed before going any further. If insulted further, they may inhale this meconium is successfully infated nothing else will have any chance of success. In a baby who is born through heavily meconium the air supply or a big leak from the mask, check the following issues: stained liquor and who is unresponsive at delivery – and only if 2,3 Consider: unresponsive it is worth inspecting the oropharynx and removing any thick particulate meconium by means of a large bore suction • Is the baby truly being supported in the neutral positionfi If the infant is unresponsive and you have the appropriate skill then intubating the larynx and then ‘hoovering out’ the upper • Is jaw thrust necessaryfi Attempting to remove meconium or other endotracheal blockages by passing a suction catheter down • Might you achieve better airway control with two people through the endotracheal tube itself is unlikely to be successful as the controlling the airwayfi Breathing If the baby has not yet responded then the next step is to ventilate the • Might there be a blockage in the oro-pharynx or tracheafi Remember the lungs will be fuid flled if the baby has made no The presence of meconium on a collapsed baby may give a clue to attempts to breathe. It is well known that other less obviously visible and then attempt to infate the lungs with air at a pressure of around substances such as blood clots, lumps of vernix or thick mucus plugs 30 cm of water aiming for an inspira to ry time of 2 to 3 seconds. The most efective Watch babies who have been successfully resuscitated for signs of way to perform chest compressions is with both hands encircling the hypoxic-ischaemic encephalopathy. Place the thumbs to gether centrally over the lower sternum with the fngers overlying the spine at the back, briskly compress the chest between fngers and thumbs at a rate of about 120 beats per minute. Air is all that is necessary for lung infation and drugs have a very limited place. The need to proceed as far as this is relatively rare – probably around 1 in 1000 births – and the length of time compressions are needed is 7 reFerenceS also relatively short – a few minutes at most. Update in Anaesthesia (2009) 25(2):65 Having given 30 to 60 seconds of chest compressions you should 68. Once again look for an increase in heart rate library/media/b4866481ef4d3dec79740f12a3a50482-Newborn-Life which indicates successful delivery of oxygenated blood to the heart. Delivery room management delivered as expected before deciding that further intervention is of the apparently vigorous meconium stained neonate: results of a needed. However, if the heart rate remains slow – less than about 60 multicenter international collaborative trial. Oropharyngeal and nasopharyngeal suctioning of meconium-stained neonates before delivery of their 7. Epinephrine (adrenaline) is traditional in these situations and, cardiopulmonary resuscitation and emergency cardiovascular if given centrally ideally via an umbilical venous cannula – does care science with treatment recommendations: Neonatal improve coronary artery perfusion pressure in animal experiments. Defning the reference range possible place for the use of alkalinising agents such as bicarbonate and for oxygen saturation for infants after birth. An advisory statement from It must be said that babies who appear to require this degree of help the Neonatal Task Force of the International Liaison Committee on to survive are at very high risk of permanent and severe neurological Resuscitation. The resulting antigen threatening condition anaphylaxis, with the exception of adrenaline, are antibody complex leads to the degranulation of mast Prompt recognition and not universally available to healthcare providers, and cells and massive chemical media to r release, which optimal management clinical guidelines were in use in only 70% of surveyed results in the classical features of: reduces adverse outcomes nations. The condition is likely to be both under IgE mediated’ responses often being labelled as simple measures are diagnosed and under-reported. Tese reactions do not useful in the management of anaphylactic reactions in children and adolescents require antigen pre-sensitization, and can involve anaphylaxis has been estimated as 10. IgE and non-IgE reactions are efective treatment in family his to ry, multiple surgeries, latex exposure and clinically indistinguishable in their presenting features anaphylaxis food allergy are all risk fac to rs. The term signifcant, with up to 10% of all reported anaesthesia ‘anaphylac to id’ has now largely been abandoned. Most fatal cases of anaphylaxis are Food allergy is the commonest cause of anaphylaxis Dept of Anaesthesia, seen in patients with asthma. G R Rodney Worldwide variation in common food allergens is Consultant pathophySioloGy seen. Of particular interest to the anaesthetist is Dept of Anaesthesia, Anaphylaxis is an IgE mediated type I hypersensitivity the association between egg allergy and propofol Ninewells Hospital and reaction, which occurs after exposure to a (discussed below). Some children outgrow their food Medical School, foreign molecule/antigen, and results in mast cell allergy; hypersensitivity to allergens such as nuts and Dundee, degranulation and histamine release. The clinical shellfsh remain throughout life and are commonly Scotland syndrome of anaphylaxis is much more complex associated with more severe reactions. E to midate hypersensitivity is exceedingly Common allergens encountered in the perioperative period include rare. Ketamine use is increasing in hospital and pre-hospital settings neuromuscular blocking agents, antibiotics and latex. Tese account and has been a common sole anaesthetic agent in the developing for the majority of perioperative reactions. Tus colloid based intravenous fuids, dye and chlorhexidine anti-septic both ketamine and e to midate provide a good anaesthetic option for solutions are all potential causative agents. Reported reactions are more likely for more than 60% of anaphylactic reactions in the perioperative to be caused by accidental intravascular injection or reaction to period. Perioperative reaction rates are now falling in areas • Intermediate risk: vecuronium, pancuronium where this has been achieved. The following groups of children are at high risk for latex allergy:17 • Low risk: atracurium and its isomer, cisatracurium • Multiple operations Controversy surrounds the risk of anaphylactic reaction to rocuronium. Some studies claim it to be a high-risk allergen • Surgery in the neonatal period while others suggest that it is an intermediate risk agent and that 13 • A to pic children increased reaction rates merely refect increased frequency of use. Non-immune histamine release is seen with atracurium and other • Spina bifda benzylquinolonium compounds. Sensitisation is thought to be due to exposure to other compounds with a quaternary ammonium Tere is also recognised cross reactivity between latex and food such ion, found in common household products such as cosmetics, as kiwi, banana and avocado. Staf should have good knowledge of latex products and the latex-free alternatives. Medical staf should use latex antibiotics free products where possible to avoid sensitisation of themselves and Antibiotics account for up to 15% of all reactions occurring under their patients. The two agents have a shared fi-lactam ring, and cross products such mouth washes, antiseptic wipes, eye drops, and as a reactivity rate of 10% between the two classes of drug is often quoted, coating for medical devices such as urinary catheters, central lines but is now discounted by many experts. Anaphylaxis to chlorhexidine has been exposure in those with previously documented anaphylaxis to either reported in those with a known allergy to chlorhexidine, but where agent. Fortunately, anaphylactic reactions to other broad-spectrum the presence of chlorhexidine was not recognised, for instance in a antibiotics such as clindamycin and gentamicin are rare. The egg-based its presentation and severity and so a high index of suspicion is constituent of propofol is a highly purifed phosphatide, lecithin, required. The vast majority of anaphylactic between propofol and egg allergy has not been demonstrated. Symp to ms and Manufacturers suggest a cautious approach is best in those with egg signs evolve within seconds or minutes of allergen exposure. The related anaphylaxis, but propofol has been widely administered to 16 chief difculty in managing perioperative anaphylaxis has often egg allergic patients without incident. Clinical criteria for diagnosing anaphylaxis (adapted bronchospasm and hypotension. In the absence of anaphylaxis is highly likely when any one of the following three skin manifestations the diagnosis can be overlooked in favour of criteria is met: an alternative event. Acute onset of illness (minutes to several hours) with involvement be missed as access for examination is limited by surgical drapes or of the skin, mucosal tissue, or both. If the child is conscious, they may initially develop • Reduced blood pressure or associated symp to ms of end hoarseness or complain of a tingling throat. Two or more of the following that occur rapidly after exposure to in children, only found in between a quarter and a third of cases.
Both studies found no significant difference in the incidence of adhesion between the active and control sides treatment 3 phases malnourished children purchase topiramate, with a follow-up period of at least 3 months medicine man 1992 generic topiramate 100mg visa. Animal Studies Animal trials also have contributed significantly to medications not to take with blood pressure meds cheap topiramate 100 mg visa our understanding of wound healing of the paranasal sinuses and there is a large number of trials that reflect this treatment jerawat di palembang order generic topiramate from india. Sheep are an ideal model as they are a large animal model where routine sinus surgical techniques can be used, and his to logically their mucosa is identical to that of 303 humans. Models of bacterial rhinosinusitis have also been developed by the blockage of the maxillary sinus ostia using Merocel, along with Bacteroides fragilis inoculation resulting in a his to logically confirmed persistent, localized bacterial 304 rhinosinusitis. Finally rabbits have well-pneumatized sinus cavities, and both their sinonasal ana to my and immunologic reactions are very similar to those of humans, 305 making them a useful animal model for the study of biomaterials. Results showed no significant 69 difference in the rate of reepithelialisation, to tal surface of ciliation, and overall 306 maturity of cilia between the packed vs non-packed sides at any time point. A further study was performed aimed at determining the effects of MeroGel vs no treatment in a sheep model of chronic sinusitis. This study created standardized mucosal injuries following by his to logical analysis of healing mucosa at 1, 2, 3 and 4 months pos to peratively. Results showed no significant difference in adhesion formation or on his to logical features of reepithelialisation, cilial height, and reciliation 240 between the 2 arms. Chi to san gel significantly improved re 220 epithelialisation, re-ciliation and cilial grade(p<0. In conjunction to this it has 307,308 been shown to have an inhibi to ry effect on fibroblast proliferation. The sheep model has also been used to examine the effects of drug delivery associated with nasal packing. Robinson et al studied the effects of prednislone impregnated MeroGel vs MeroGel alone and found no difference. Finally growth fac to rs have also been shown to be important in epithelialisation and collagen 227 deposition, including insulin-like growth fac to r. Mice models There is only one study using a murine model to examine the effects of biomaterials. Findings were of induced bone formation within 310 the sinonasal cavity, concluding that MeroGel may have osteogenic potential. Rabbit models Maccabee et al studied the effects of MeroGel in 6 self controlled rabbits by denuding the maxillary sinuses and performing his to logical analysis of the regenerating mucosa. At 2 weeks pos to peratively the MeroGel sinuses showed extensive fibrosis when compared to control sinuses, with minimal reabsorption of the biomaterial along with incorporation of the biomaterial within the regenerating 311 mucosa. Proc to r et al confirmed these findings, analysing the effects of MeroGel in a rabbit model. Results showed that MeroGel caused significant stenosis of the 312 ostia over a 2-3 week followup. Maccabee et al studied the effects of FloSeal in 6 self controlled rabbits by denuding the maxillary sinuses and performing his to logical analysis of the regenerating mucosa. At 2 weeks pos to peratively FloSeal sinuses showed extensive fibrosis when compared to control sinuses, with minimal reabsorption of the biomaterial 311 along with incorporation of the biomaterial within the regenerating mucosa. Mi to mycin C has also been investigated in the rabbit model, with one pilot study showing that increasing concentrations of Mi to mycin C can delay healing of an 314 intranasal antros to my (0. It is important to note however that these trials were conducted in healthy rabbits without chronic rhinosinusitis, perhaps explaining the discrepancies between findings of human studies. There are two published studies investigating the effect of retinoic acid treated mucosa in rabbits. These findings 317 were also supported by Hwang et al, again involving the healthy rabbit model. Two prospective, controlled rabbit trials suggested that MeroGel increases fibrosis and is incorporated within regenerating mucosa, and another showed that MeroGel displayed osteogenic potential. Again the rabbit model has shown that FloSeal increases fibrosis and is incorporated within the healing mucosa, a finding supported by a second independent study. However one prospective trial suggests that Gelfilm stenting results in significantly more adhesions. Finally there is only 1 uncontrolled prospective trial investigating the effects of surgiflo/thrombin combination, with no adhesions observed by the authors. Sepragel sinus appears to have no objective effect on immediate hemostasis, and wound healing effects unknown. In summary the literature suggests that the use of dissolvable agents to improve wound healing is largely unfounded and the anticipated beneficial effect of nasal packing is wishful thinking rather than a clinical reality. In some cases the use of dissolvable agents actually has an adverse effect on the wound healing processes. There is no commercially available product that improves wound healing when compared to no treatment at all. Recent animal studies indicate that Chi to san may be of benefit but further research is required before recommendations can be made. Endonasal microscopic techniques to the sella turcica rapidly became the preferred approach following the introduction of the operating microscope in 1951. The introduction of the surgical endoscope has seen a rejuvenated interest in to the paranasal sinus and endonasal skull base ana to my and the endoscopic approach to pituitary and other skull base tumours is rapidly being adopted as the standard of care by o to laryngologists and neurosurgeons 323 worldwide. The popularity of endonasal techniques is largely due to the well recognized advantages including the avoidance of external skin incisions, minimal sacrifice of intervening structures, improved visualization, reduced pos to perative 324 pain and shorter hospital admissions. All of this demonstrates that with the increasing subspecialisation of endoscopic transphenoidal surgery, it increasing the likelihood a specialist endoscopic skull base surgeon will have to manage a carotid artery injury at some stage. Patients At Risk Prevention of the catastrophic bleeding scenario is better than treatment. In the 3 patients reported by Koitschev et al, all 3 patients died as a result of uncontrolled haemorrhage, perhaps as a result of a larger 334 defect of the vessel wall with a consecutively higher blood loss. Additionally patients with acromegaly tend to have more to rtuous and 123,335 ectatic carotid arteries. These features may cause more fibrosis and adherence to the carotid artery, or may simply reflect a more aggressive attempt at complete resection of invasive lesions. Bejjani et al demonstrated that vasospasm occurred in 9 of 470 patients undergoing skull base tumour dissection. In this series vasospasm manifested as altered mental status and/or hemiparesis with risk fac to rs including preoperative embolization, tumour size, vessel encasement/narrowing and to tal operative time. They describe 1 fatal, and 2 non-fatal cases as a result of carotid spasm and thrombosis following endonasal 123 transphenoidal surgery. Massive bleeding leads to a loss of orientation and an obscured surgical field often resulted in the surgeon blindly attempting nasal packing in order to control the haemorrhage. The advantages of the ‘2 surgeon’ skull base team allows for dynamic handling of the endoscope, rather than the single surgeon scenario. Currently there is no prospective experience or scientific enquiry in to the techniques required to control such a large volume bleed, leaving the surprised surgical team to manage the event without prior training or experience. As part of this thesis we have developed a reproducible animal model for the carotid artery catastrophe that recreates the intranasal confines of the human nasal cavity, paranasal sinuses and nasal vestibule (chapter 8). Experience with this model has 81 allowed a number of important surgical steps to be identified that will aid the surgical team in controlling the haemorrhage and maintain vision of the injury site (chapter 9). Intra-operative Haemostatic Techniques Every surgical team should have a plan in place should this unexpected complication occur; formulating and executing a plan of action during a crisis is difficult. In good collateralization or contralateral compensation the bleeding is likely to still be rapid. Ligation of the internal and external carotid arteries would not only waste time but also block the interventional radiologists access to the site of injury. In the event of unexpected massive bleeding during endonasal surgery then immediate packing is required. Some authors advocated for head elevation, and 339 controlled hypotension to reduce the hemorrhage. These measures are likely unnecessary considering the immediate and significant hypotension that will result from massive bleeding whilst the anaesthetic team is trying to implement active 340 resuscitation. If large bore suction devices and the immediate state of hypotension are not enough to keep pace with the bleeding and allow nasal packing then ipsilateral common carotid artery compression is frequently advocated to slow the 124,327,339,341 bleeding rate and can aid the accurate placement of nasal packing. Regarding blood pressure control, Kassam et al, Solares et al and Pepper et al all recommend maintaining normotension through resuscitative measures and fluid 82 136,173,342 replacement in order to maintain contralateral cerebral perfusion. However, normotension is unlikely to be achieved until the haemorrhage has been controlled. Once vascular control is assured then attention should focus on maintaining adequate cerebral perfusion. A review of the literature demonstrates that gauze packing is overwhelmingly the most frequently used material, likely due to its availability and easy of use.
Subtle cues such as ‘she’s not normally like this’ and ‘I’ve never seen him so unwell’ should be ‘think sepsis’ particularly when faced with a patient with one or more risk fac to symptoms west nile virus topiramate 200 mg with amex rs treatment tendonitis discount topiramate 200mg with visa. The frst version was a highly validated to symptoms 0f ms order topiramate with amex ol in the identifcation of deterioration from any cause medicine identifier pill identification order cheap topiramate on line. Although any infection can give rise to sepsis, the most common sources are shown in Box 3. Meningitis 1% Others 2% Here is where we really see the need for formal, ‘research-centred’ defnitions, and distinct pragmatic solutions to aid those working in front line healthcare. All that is needed is a reasonable clinical suspicion of infection, so a chesty cough with green sputum, or i. Ask a senior, make sure someone orders tests such as a chest X-ray, and revisit the diagnosis once you Measurement Score Measurement Score have more information. We include here an extract of those algorithms, defnition created for the most part for use by Critical Care specialists. The risk here is the ready availability of clinical staf with sufcient eperience and gestalt. It’s a now have access to pulse oximetry (for adults), it would be difcult to accurately measure hourly urine to ol designed to help you to get on and ensure the patient gets the treat outputs in the back of an ambulance. Organisations who had adopted Red Flag Sepsis were used to measuring lactate at the bedside at the time of presentation – many such organisations retain lactate measurement as a Red Flag. Amber Flags, bloods should be sent in addition to ensuring review by a senior clinician. Actions will vary according to your clinical setting – for a General Decision-making, once Amber Flag(s) have been identifed, is based upon clinical judgement and should Practitioner or Community Nurse, this might be to call 999 and take in to account both patient and environmental fac to rs. Discharge from hospital, possibly with oral antibiotics, may be appropriate with safety netting and consideration given to a scheduled review. Health professionals outside hospital should consider whether the patient can safely be cared for in the community or requires hospital assessment (with appropriate documentation of the decision and If neither a Red Flag nor an Amber Flag are present, this indicates a low risk of adverse outcome from safety netting if the patient is to be managed in the community). Other conditions should be considered, and recommends that a single Amber Flag should prompt consideration of the need for blood tests ( to include standard pro to cols followed. If care in the community is considered suitable, then verbal and written lactate, Full Blood Count, urea and electrolytes, C-reactive Protein, liver function tests and enzymes and safety netting instructions should be provided where appropriate. Within this chapter, we have explored the balance between the need for an ‘ofcial’ defnition of sepsis – primarily for use in Critical Care, and important for ensuring we are entering the right patients in to clinical It seems that a formal diagnosis of septic shock is outside the remit of most people working outside trials – and a more pragmatic, ‘bedside’ defnition. A search for the source of infection is critically important to ward ensuring that we use antimicrobial agents responsibly by allowing us to target treatment with evidence-based, often narrower spectrum choices of agents. These might include a productive cough, tachypnoea, noisy breathing (sometimes audible from the end of the bed), or respira to ry distress. Diagnosis Pneumonia can be confrmed by a chest X ray showing new shadowing that is not due to any other cause (such as pulmonary oedema or infarction). In addition, some pneumonias can be considered “atypical” (caused by uncommon microorgansims). If you suspect your patient may have an atypical pneumonia it is otherwise healthy young men. More than half of pneumonia-related deaths occur in people older than 84 ‘routine use’ and never for moni to ring urine output in ambula to ry patients) years. Intra-abdominal infections commonly arise from the biliary pyelonephritis (infection of the kidney and renal pelvis), cystitis (infection of the bladder), urethritis tract. Infection may spread to surrounding tissues (for example, perinephric abscess) or is ischaemic), bacteria can ‘translocate’ across the lining of the bowel in to the bloodstream, precipitating to the bloodstream. In complicated intra-abdominal infections, the infection progresses from a single organ and afects the peri to neum, which can lead to the formation of intra-abdominal abscesses or difuse peri to nitis. Peri to neal contamination may result from mishandling of bowel contents during surgery, or from Symp to ms reported can include dysuria, frequency, ofensive-smelling or discoloured urine, loin pain and trauma or a spontaneous perforation (for example, appendicitis, perforated ulcer or diverticulitis). A positive urine dipstick in the absence of symp to ms vasodilation) or altered mental state. Symp to ms tend to be localised initially (such as in Common organisms causing urinary tract sepsis are gram-negative bacteria such as E. Symp to ms of meningococcal sepsis include some of the above plus rigors, with rapidly spreading erythema, blistering, or even skin necrosis. Worsening carefully marking the margins of the erythema at presentation can help assessment of whether the initial neurological signs may indicate the development of cerebral oedema or hydrocephalus (raised antibiotic therapy is efective or not. Whatever the cause, the presence of a purpuric rash in the Diagnosis context of suspected infection is a medical emergency and demands the highest level of skill and experience available. Swabs taken for culture may confrm the organism involved – treatment will need to be started before results are available. If there is doubt about Beware of rapidly spreading cellulitis, or exquisite pain which is disproportionate to the clinical fndings. Necrotising fasciitis has a high associated mortality and requires rapid and extensive debridement of the afected area in It is vital not to delay treatment. If suspected, the most senior available member of the team should be meningitidis) such as cefotaxime/ceftriaxone should be given immediately. However, for the individual patient we must not let our guard down and retain a high index of suspicion. Additional Although line sepsis accounts for only around 1% of episodes, it is almost always avoidable so should not be dismissed as unimportant. It is important to ask about trauma or recent instrumentation to the joint such as arthroscopic surgery. It is important to liaise with orthopaedic • Induration thrombophlebitis • Palpable venous cord surgeons and/or rheuma to logists. In many cases a joint washout by arthroscopy is warranted (source • Pyrxia control), and should be completed within the frst six hours (and ideally sooner). They may have signs of heart failure such as raised jugular venous pressure, peripheral oedema and pulmonary congestion. An echocardiogram should be requested to look for vegetations, but absence of these does not exclude the diagnosis. It can however be very difcult to treat, and may take many weeks of antibiotic therapy. This is not a common condition • Sepsis is a multi-disciplinary condition – enlist expert help early. Several fac to rs are likely to be at play, including: • the type of pathogen causing the infection – some are more prone to triggering an aggressive response than others (they’re more ‘virulent’) • the number of pathogens present, and where in the body they are • Individual or ‘host’ fac to rs: these are determined by both genetics and by acquired conditions, which may predispose to a disordered immune response. The skin around the injury quickly becomes red, it swells slightly; it is also hot to to uch and is painful. With capillary leakage, patients may appear oedema to us, have a runny nose, dizziness, diarrhoea and/or vomiting. The body ‘senses’ that injury has occurred, which it can fx by mobilising white blood cells to the site of injury to neutralise any pathogens. A full description of the pathophysiology of sepsis is beyond the scope of this manual: Amplifcation Media to r molecules Function Capillary Leakage Nitric oxide causes and maintains vasodilation. This Nitric oxide helps to make capillaries more permeable (‘leaky’) Bradykinin is responsible for the pain at the site of infammation (preventing us from damaging ourselves Bradykinin further), and is also involved in vasodilatation and making capillaries more permeable Complement proteins act directly to neutralise Vasodilation Complement proteins pathogens, mobilise white blood cells and amplify the Diagram: the efects of infammation immune response Thrombin helps clot formation by turning fbrinogen Thrombin in to fbrin, and is involved in nitric oxide production i. This is necessary to mobilise white blood cells, fbrin and platelets to where they are needed. However, as the above table demonstrates, infammation is mediated by a complex set of molecules which are all inter-related. It is therefore inevitable that processes will go wrong and it is understandable why sepsis can have such a rapid progression and poor prognosis. This is largely known as the ‘humoral’ component of the immune response, but to neutralise complex infections requires a cellular component to o. Some, such as neutrophils, act by releasing ‘granules’ which contain enzymes with which to attack pathogens. B cells make antibodies, which can bind to pathogens and accelerate their destruction. White blood cells are the second line of defence, and are vital to ensuring a sustained attack In essence, these processes mean that the lungs are stif and cannot transfer oxygen and carbon dioxide on invading pathogens. This mechanism is the body’s way of meeting the oxygen demand of organs, muscles and tissues, as a result of a low circulating volume despite the stif lungs.
Collagen products: microfibrillar collagen products such as Avitene and Gelfoam are frequently utilized as local to symptoms 0f brain tumor discount topiramate line pical hemostatic agents during endoscopic surgery and have the advantages of easy to medicine quinine order topiramate 200 mg on line use and at a low cost treatment hepatitis c cheap 100mg topiramate with visa, even though most studies 190 medicine names cheap topiramate 200 mg otc,191 suggest that fibrin glue maybe more a more effective haemostat. It has also been shown to be effective at holding dural grafts in place following skull base 192 reconstructions. However, there is concern regarding its potential for disease transmission and antibody formation, which has driven the development of a recombinant thrombin, with comparable 194 efficacy to bovine thrombin. Hyaluronic Acid/Carboxymethylcellulose: Hyaluronic acid (Sepragel sinus) is a viscoelastic gel containing polymers of highly purified forms of hyaluronic acid and has been investigated for immediate hemostasis by Frenkiel et al. Results showed that there was no significant difference between the to tal blood loss when comparing the Sepragel sinus side vs the no treatment side, however a subjective general 195 improvement of hemostasis was noted with the intervention side. Nursing staff reported persistant oozing in 20% of 196 patients, however no patient required intervention. It has been shown to have moderate haemostatic capabilities, however despite its popularity since this time there are still no studies that compare surgicel to no treatment. All packing agents were equally effective with 200 no incidence of pos to perative epistaxis in any of the treatment arms. Platelet Gel: Platelet gel is a fibrin tissue adhesive product manufactured from centrifugation of au to logous whole blood giving a platelet rich plasma. It has the advantages of eliminating the risk of potential virus transmission and antibody formation to coagulation fac to rs. Use in the rhinology community commenced in 2001, following a presentation to the American Rhinologic Society. Antifibrinolytics: these agents have been in use since the 1960s and are now in 201,202 widespread use within the medical field. These agents function by blocking the lysine binding sites on plasminogen and preventing the activation of plasmin, functioning to preventing fibrinolysis and stabilizing the blood clot. Results showed that to pical epsilon-aminocaproic acid was ineffective at achieving hemostasis compared to saline, however tranexamic acid at low dose (100mg) improved hemostasis significantly (p<0. Of specific interest is this is only the second study in the literature to use an objective surgical grade score to moni to r the hemostatic efficacy. Polyethylene Glycol: There are a number of polyethylene glycol products on the market for intranasal use, including CoSeal and Nasopore. Chi to san: Chi to san is prepared from chitin, a polymer that is found in a large number of natural sources including crustaceans, fungi, insects, annelids, molluscs and 208 coelenterata. Currently chi to san is used as a preservative to foods, an antimicrobial coating on fruits and vegetables for human consumption, a coating for seeds prior to planting, a hydrating cosmetic product as well as an additive to shampoos and 209 to othpaste. Chi to san has long been known to be an effective hemostatic agent, Klokkevold et al reported that chi to san solution added to bilateral to ngue incisions in a rabbit model resulted in a 43% improvement in bleeding time as compared to 46 210 controls. Aguilera et al found, in a high flow arterial wound model in swine, that a chi to san acetate dressing was 100% effective for maintaining hemostasis for a 211 period of at least 30mins, compared to a 21% effectiveness in the gauze arm. Preparations of chi to san have been shown to initiate hemostasis independent of platelets or 212 coagulation fac to rs. Scanning electron microscopy has shown that chi to san 213 increases the affinity of red blood cells. Chi to san has been used within the nasal cavity as a carrying agent to deliver medications such as prednisolone, vaccines, growth hormones, anti-inflamma to ry 214-219 agents, antibiotics and insulin. However the effects of this gel on haemostasis remains unknown, and has been the subject of analysis in this thesis (chapter 6 and 7). Cyanoacrylate: Tissue adhesives have been popular within medicine for their success in closing lacerations and surgical incisions. They are also reports of their 221,222 success in achieving haemostasis on the skin. There is also a porcine epistaxis model where cyanoacrylate glue has been shown to be beneficial in controlling nasal 223 bleeding in heparinised animals. The main reason for repair is to protect the organ from repeated injury, prevent the loss 226 of vital substances and to replace or repair damaged ana to mical structures. The nasal mucosa is a physical barrier to foreign materials, and also aids in conditioning the inhaled air ready for the lower airways. The nasal epithelium lies on the basement membrane, which is situated on the lamina propria. The lamina propria consists of 2 layers of seromucous glands: a superficial layer that is situated just beneath the nasal epithelium, and a deep layer beneath the vascular layer. Beneath the basement membrane lies the lymphoid layer, consisting of plasma cells and lymphocytes. The vasculature of the nose contains specialized capacitance vessels, allowing the nasal mucosa to regulate airflow, condition the inspired air and allow an 227 organized first line of immune defense. The nasal epithelium consists of pseudostratified columnar epithelium and is composed largely of ciliated cells, non ciliated cells, goblet cells and basal cells. These 4 main cell types allow for mucus production and transport, resolution of surface materials, and the formation of new 227 epithelial cells. Elegantly summarized by Watelet et al, the outcome of wound healing lies on a continuum between complete replacement of injured tissue with newly regenerated 227 cells or with scar tissue formation. Growth fac to rs and cy to kines are the media to rs responsible for the coordination of processes involved including inflammation, cell proliferation, matrix deposition and remodelling. Growth fac to rs activate their target cells by binding to their corresponding high-affinity surface membrane recep to rs. These stages are the coagulation phase, the inflamma to ry phase, and proliferative phase and 226,227 finally the maturation/remodelling phase. Surgical trauma to the nasal epithelium results in the obliga to ry rupture of vessels and their exposure of subendothelial collagen to platelets. The result is activation and aggregation of platelets to form a haemostatic plug, with the release of vasoactive substances such 230 as histamine, bradykinin and sero to nin. These vasoactive substances allow vasoconstriction to occur over the next 5-10 minutes, which assists in allowing the haemostatic plug to develop, and prevent blood loss. The locally formed fibrinous clot at the end of the coagulation cascade serves as an important scaffolding for migrating cells that are the hallmark of the inflamma to ry 231 phase: such as neutrophils, monocytes, fibroblasts, and endothelial cells. In fact 51 inadequate clot formation is associated with impaired wound healing due to either 232,233 decreased adhesion of cells in to the area or decreased chemotaxis. Inflamma to ry Phase this phase is characterised by an increase in vascular permeability due to inflammation and release of prostaglandins. These locally released cy to kines and growth fac to rs result in the stimulation of predominantly polymorphonuclear neutrophils during the first 24-48 hours. After the first 72 hours neutrophils begin to be replaced by monocytes over the next 3-5 days, then 226 becoming activated macrophages. Their role in debridement, matrix synthesis and 234 angiogenesis is essential in the continuation of wound healing. If a prolonged inflamma to ry phase occurs, as may during a pos to perative microbial infection, this 230 may result in an excited phase of fibroplasia. Proliferation Phase the proliferation phase lasts between 3-21 days and is characterised by the proliferation of fibroblasts, endothelial cells and epithelial cells. It is the macrophages located in the nasal lamina propria that provide the continuing source of cy to kines 227 necessary to stimulate the proliferation of these cells. Cy to kines from platelets and 52 macrophages are responsible for the migration and attraction of fibroblast to the wound area. This phase is characterised by the corresponding increased blood flow to the healing tissue and angiogenesis, and is recognised by the development of granulation tissue (consisting of fibroblast, macrophages and neovasculature). Once the nasal fibroblasts have migrated to the area they then switch their major function to protein synthesis, reaching their maximum in the first 2 weeks, with wound 226 collagen levels at their highest within 3 weeks following the injury. Epithelial regeneration and migration begins from the adjacent uninjured areas, and begins within a few hours, at an estimated velocity of 4 µm/hour within the nasal 235,236 cavity. The epithelial cells at the wound edge slowly develop cy to plasmic extensions in to the wound area. Four different processes occur simultaneously to allow for re-epithelialisation: epithelial cell migration, multiplication, reorientation and differentiation, all occurring from the respira to ry basal cells (the main source of 237 epithelial cells). Whilst epithelial regeneration occurs rapidly, ciliogenesis and 238-240 differentiation can take several months. Maturation/Remodelling Phase Nasal extracellular matrix remodelling, cell apop to sis, cell apop to sis and wound 227 remodelling may continue for up to 6 months after surgery, however a full thickness mucosal injury may take much longer, and not be completely mature for 241 more than 18 months.
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