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Biomedical subjects

Geoffrey K Isbister

Publications and source records attributed to Geoffrey K Isbister.

At least 73 records · Page 4Linked to original sources

Bites by spiders of the family Theraphosidae in humans and canines.

Spiders of the family Theraphosidae occur throughout most tropical regions of the world. There have only been three case reports of bites by these spiders in Australia. The aim of this study was to describe the clinical effects of bites by Australian theraphosid spiders in both humans and canines. Cases of spider bite were collected by the authors over the period January 1978-April 2002, either prospectively in a large study of Australian spider bites, or retrospectively from cases reported to the authors. Subjects were included if they had a definite bite and had collected the spider. The spiders were identified by an expert arachnologist to genus and species level where possible. There were nine confirmed bites by spiders of the family Theraphosidae in humans and seven in canines. These included bites by two Selenocosmia spp. and by two Phlogiellus spp. The nine spider bites in humans did not cause major effects. Local pain was the commonest effect, with severe pain in four of seven cases where severity of pain was recorded. Puncture marks or bleeding were the next most common effect. In one case the spider had bitten through the patient's fingernail. Mild systemic effects occurred in one of nine cases. There were seven bites in dogs (Phlogellius spp. and Selenocosmia spp.), and in two of these the owner was bitten after the dog. In all seven cases the dog died, and as rapidly as 0.5-2h after the bite. This small series of bites by Australian theraphosid spiders gives an indication of the spectrum of toxicity of these spiders in humans. Bites by these spiders are unlikely to cause major problems in humans. The study also demonstrates that the venom is far more toxic to canines.

Adult↗

Australian scorpion stings: a prospective study of definite stings.

There is little information on scorpion stings in Australia. The aim of this study is to describe the circumstances and clinical effects of stings by Australian scorpions. Cases of scorpion stings were collected prospectively from calls and presentations to Australian poison information centres and emergency departments from February 2000 to April 2002. Only definite scorpion stings where the scorpion was immediately collected and expertly identified were included. There were 95 patients, 33 males and 62 females, with a mean age of 32 (SD 19.5; range 1-71) and 23 children (age<15 years). Three families of scorpions caused all stings: Buthidae (79), Bothruiridae (11, all Cercophonius spp.) and Urodacidae (five, all Urodacus spp.). The majority of stings (76%) were by one genus of scorpion Lychas spp. Seventy one percent of stings occurred between 6pm and 8am and 82 (86%) occurred indoors. Sixty percent of stings occurred on distal limbs. The median duration of effects was 6 h (interquartile range (IQR): 1-24 h). Immediate localised pain occurred in all cases and was severe in 76 cases (80%). Other local effects included red mark/redness (66%), tenderness (35%), numbness (12%) and paraesthesia (11%). Minor systemic effects (nausea, headache and malaise) occurred in 11% of cases. There were no deaths or major systemic envenoming. Less severe effects were observed for the larger Urodacus species, compared to Lychas spp. Scorpion stings in Australia do not appear to cause severe or life-threatening effects, even in children. This differs from other parts of the world, where severe envenoming is reported. The major clinical effect is severe pain, consistent with other scorpion stings. Most stings occurred indoors and at night.

Adolescent↗

A prospective study of definite bites by spiders of the family Sparassidae (huntsmen spiders) with identification to species level.

Spiders of the family Sparassidae occur on most continents in tropical and temperate regions of the world. They are large Araneomorphae (modern spiders) which are often feared. There are few reports of confirmed sparassid bites and some suggest that particular genera (Neosparassus) can cause severe effects. This study investigated the circumstances and clinical effects of bites by Australian sparassid spiders with correlation to taxonomic species level. Cases were recruited prospectively from calls to Australian poison information centres and two emergency departments. Patients were included if there was a clear history of bite and the spider was caught, and were followed up over a week. There were 173 patients with spider injuries and 168 with definite bites by sparassid spiders over a 27 month period. Ninety-five percent of bites were by spiders from four genera: Isopeda (32%), Isopedella (21%), Neosparassus (27%) and Heteropoda (14%); other genera included Delena and Holconia. The seasonal and diurnal distribution of bites differed between genera, although the majority occurred in warmer months in daylight hours. Seventy-six percent of bites occurred because the spider was interfered with (picked up, dressing or picked up an object with the spider) consistent with the behaviour of most of the family requiring provocation to bite. Ninety-five percent of bites occurred on limbs, 82% on distal limbs, again consistent with handling the spider. Pain/discomfort occurred in all cases, and was severe in 27%. The median duration of pain was 5 min which was significantly less than other spiders. Puncture marks (40%) or localised initial bleeding (35%) occurred in 54% of bites, and both occurred significantly more often in all sparassid bites compared to all other spider bites (p<0.0001). Swelling occurred in 16%, itchiness in 14% and redness/red mark in 57% of cases, the latter significantly less common than other spiders (p=0.0002). Systemic effects occurred in 4% of bites and were minor (nausea and/or headache). There were no cases of necrotic ulcers or allergic reactions. There were four cases with features consistent with local infection. Bites by sparassid spiders cause minor effects, characterised by immediate and transient pain, associated with bleeding, puncture marks and local redness. The mechanism of effects appeared to be trauma rather than envenoming. There were no major differences between genera, and Neosparassus spp. did not cause major effects.

Adolescent↗

Quetiapine poisoning: a case series.

STUDY OBJECTIVE: We describe the effects of quetiapine in overdose. METHODS: Quetiapine poisonings were identified from a prospective database of poisoning admissions to a regional toxicology service. Data extracted included details of ingestion, clinical features, investigations (including ECG), and other outcomes (length of stay and ICU admission rate). RESULTS: There were 45 cases of quetiapine overdose, of which 18 patients with quetiapine assay results were included. Median length of stay was 35 hours (interquartile range [IQR] 14 to 42 hours) for the 18 patients, and 9 were admitted to the ICU. The median ingested dose was 3.5 g (IQR 1.7 to 6.2 g), and reported ingested dose was highly correlated with estimated peak drug concentration (r(2)=0.84; P<.0001), confirming patient-provided history of ingestion. Seizures occurred in 2 patients, delirium occurred in 3 patients, and mechanical ventilation was required in 4 patients. No arrhythmias or deaths occurred. Six of the 18 patients ingested quetiapine alone, with a median length of stay of 35 hours, and 3 were admitted to the ICU. In 1 patient who ingested 24 g, hypotension and seizures occurred. For 10 patients for whom ECGs were available and who had ingested no cardiotoxic drugs, tachycardia occurred in 8 patients. For these 10 patients, the mean corrected QT (QTc) interval was increased at 487 ms, but the mean uncorrected QT interval was 349 ms. Reported dose and peak quetiapine concentrations were significantly associated with ICU admission and length of stay more than 24 hours. A reported dose less than 3 g and a Glasgow Coma Scale score not less than 15 predicted patients not requiring ICU admission or length of stay more than 24 hours. CONCLUSION: Quetiapine overdose causes central nervous system depression and sinus tachycardia. In large overdoses, patients may require intubation and ventilation for associated respiratory depression. Although a prolonged QTc occurs, its clinical significance is unclear because it is most likely caused by an overcorrection caused by the tachycardia. In our experience, a reported dose of less than 3 g for patients who are not drowsy (with a Glasgow Coma Scale score of 15) at least 4 hours after ingestion and who did not coingest another toxic agent defined a group not requiring ICU admission or inpatient admission greater than 24 hours.

Adult↗

Valproate overdose: a comparative cohort study of self poisonings.

AIMS: Based on individual case reports of massive overdoses, valproate is often regarded as having significant toxicity. This study aimed to describe the epidemiology of valproate poisoning and the spectrum of its clinical effects. METHODS: Consecutive valproate poisonings were identified and compared with other anticonvulsant overdoses and all other poisonings, from a prospective database of poisoning admissions presenting to a regional toxicology service. National prescription data for the same period were obtained. RESULTS: There were 79 patients with valproate poisoning from January 1991 to November 2001, 15 cases with valproate alone. Of the 15 cases, drowsiness occurred in two patients (both taking> 200 mg kg-1), vomiting occurred in four and tachycardia in five. In patients co-ingesting other medications, moderate to severe effects were consistent with the co-ingestants. There was one death not directly related to valproate. One patient had metabolic acidosis and thrombocytopaenia consistent with severe valproate toxicity. Comparison of valproate, carbamazepine, phenytoin and control groups showed that length of stay for both phenytoin and carbamazepine was significantly longer than for valproate (P < 0.0001), and there was a significantly increased risk of intensive care unit admission for carbamazepine vs valproate (OR 2.73; 95% CI 1.22, 6.28; P = 0.015). Although valproate prescriptions increased over the 10 years, there was relatively greater increase in the incidence of valproate poisoning. The odds of a valproate overdose in 1992 compared with carbamazepine were 0.29 (95% CI 0.07, 1.28; P = 0.141), but in 2001 were 2.73 (95% CI 1.38, 5.39; P = 0.004). CONCLUSIONS: Valproate causes mild toxicity in the majority of cases. Massive overdoses of greater than 400 mg kg-1 can cause severe toxicity, but these are uncommon. The older anticonvulsants phenytoin and carbamazepine remain a greater problem than valproate in overdose.

Adult↗

Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity.

AIMS: To investigate the spectrum of toxicity of moclobemide overdose, the occurrence of serotonin toxicity, and to estimate toxicokinetic parameters. METHODS: All moclobemide overdoses presenting over a 10-year period to the Hunter Area Toxicology Service were reviewed. Clinical features, complications, length of stay (LOS) and intensive care (ICU) admission rate were extracted from a standardized, prospectively collected database. Comparisons were made between moclobemide alone and moclobemide with a serotonergic coingestant poisoning. Serotonin toxicity was defined by a combination of Sternbach's criteria and a clinical toxicologist's diagnosis. In five patients serial moclobemide concentrations were measured. Time to maximal plasma concentration (Tmax), peak plasma concentration (Cmax) and terminal elimination half-lives were estimated. RESULTS: Of 106 included patients, 33 ingested moclobemide alone, 21 ingested moclobemide with another serotonergic agent (in some cases in therapeutic doses) and 52 ingested moclobemide with a nonserotonergic agent. Eleven (55%) of 21 patients coingesting a serotonergic drug developed serotonin toxicity, which was significantly more than one (3%) of 33 moclobemide-alone overdoses (odds ratio 35, 95% confidence interval 4, 307; P < 0.0001). In six of these 21 cases severe serotonin toxicity developed with temperature >38.5 degrees C and muscle rigidity requiring intubation and paralysis. The 21 patients had a significantly increased LOS (34 h) compared with moclobemide alone overdoses (12 h) (P < 0.0001) and a significantly increased ICU admission rate of 57% vs. 3% (P < 0.0001). Time to peak plasma concentration was delayed in two patients where prepeak samples were obtained. Cmax increased slightly with dose, but all three patients ingesting > or = 6 g vomited or had charcoal. The mean elimination half-life of moclobemide in the five patients in whom serial moclobemide concentrations were measured was 6.3 h and elimination was first order in all cases. There was no evidence of a dose-dependent increase in half-life. CONCLUSIONS: The effects of moclobemide alone in overdose are minor, even with massive ingestions. However, moclobemide overdose in combination with a serotonergic agent (even in normal therapeutic doses) can cause severe serotonin toxicity. The elimination half-life is prolonged by two to four times in overdose, compared with that found in healthy volunteers given therapeutic doses. This may be a result of wide interindividual variation in overall elimination, also seen with therapeutic doses, but appears not to be due to saturation of normal elimination pathways.

Adult↗

Suspected snakebite: one year prospective study of emergency department presentations.

AIM: Snakebite is an uncommon, but potentially life-threatening condition. The more common clinical scenario is suspected snake-bite. Our aim was to characterise the epidemiology, diagnosis and management of patients with suspected snakebites. METHODS: Prospective cohort study of patients presenting with suspected snakebites to a tertiary referral hospital serving a large rural region in tropical northern Australia where a standard admission protocol for suspected snakebites is used. RESULTS: Of 70 suspected snakebite cases, there were 45 definite bites: three severe envenomings (two western brown snakes [Pseudonaja nuchalis] and one mulga snake [Pseudechis australis]); seven mild/moderate envenomings by other snakes, two non-envenomings by identified P. nuchalis, five bites by identified non-venomous snakes and 28 definite bites without envenoming. The remaining 25 cases were either suspected bites (8), unlikely bites (15) and two people hit by snakes. Definite snake-bites occurred throughout the year, peaking in May and December. There were three severe envenomings (mainly coagulopathy), requiring antivenom treatment, but no deaths or major complications. Most patients had appropriate investigations. Of 47 venom detection kit swabs collected, 34 were not tested, venom was not detected in nine and was positive in the three envenomings with one false-positive tiger snake. Whole blood clotting time was highly sensitive for procoagulant coagulopathy and envenoming in this study. Median length of time from the bite to discharge was 20 h (interquartile range: 12-27). CONCLUSIONS: The study shows that although suspected snakebite was common, severe envenoming occurred in less than 5% of cases. The study supports the proposition that a structured approach and admission policy of suspected snakebites leads to the appropriate management of severe envenoming, with no cases discharged early and no cases of non-envenoming treated with antivenom.

Adolescent↗

Presumed Angel's trumpet (Brugmansia) poisoning: clinical effects and epidemiology.

OBJECTIVE: To investigate the pattern and epidemiology of anticholinergic plant poisoning, and to characterize its time course and clinical features. METHODS: We reviewed all anticholinergic plant poisonings using a prospective database of all poisonings admitted to a major toxicology unit in Australia. All patients that presented with anticholinergic plant poisoning between July 1990 and June 2000 were included. Patient demographics, details of poisoning, diagnostic clinical features, adverse effects (seizures, arrhythmias, hypotension, accidental injury), and treatments required were obtained. Important diagnostic features were analysed and compared to previous studies. RESULTS: Thirty-three patients were presumed to have ingested Brugmansia spp. (Angel's trumpet) based on their description of the plant; median age 18 years (interquartile range 16-20); 82% males. Thirty-one ingested a brewed tea or parts of the plant (flower). Thirty-one used it recreationally. Common clinical features were: mydriasis (100%), mean duration 29 h (SD 13) and delirium (88%) with a mean duration of 18 h (SD 12). Tachycardia only occurred in 11 of the 33 patients (33%). In 24 patients where the time of ingestion was certain, 7 of 8 (88%) patients presenting within 5 h had tachycardia and only 5 out of 16 (31%) presenting after 5 h had tachycardia. There were no deaths, seizures or arrhythmias (excepting tachycardia). One patient had hypotension and two sustained accidental traumatic injuries. Nineteen patients required sedation, mainly with benzodiazepines. Physostigmine was used diagnostically in eight cases. CONCLUSIONS: Anticholinergic plant abuse is sporadic in nature. Most cases were moderate in severity, requiring sedation only, and severe toxicity was rare. Mydriasis and delirium were the commonest features, the later having important implications for management.

Adolescent↗

Nefazodone poisoning: toxicokinetics and toxicodynamics using continuous data collection.

Nefazodone overdose has been reported infrequently. The commonest effects reported are drowsiness, nausea, dizziness, and vomiting, less commonly hypotension and bradycardia. We report a case of single-agent nefazodone poisoning. Serial drug concentrations were taken for quantification of parent drug and metabolites. Clinical findings were documented every 1 to 2 hours. We modeled both the toxicokinetics of nefazodone and correlated this with clinical effects and electrocardiograph (ECG) abnormalities. A 16-year-old female took 2.4 g of nefazodone. She had significant drowsiness in the first 6 hours, associated with hypotension (systolic BP < 90 mmHg; lowest BP 70/30 mmHg) for 18 hours, and mild bradycardia (slowest rate of 56 bpm). She had a prolonged QT/QTc which normalized over 24 hours. She was given charcoal and intravenous fluids and was observed carefully, recovering with no problems. The terminal elimination half-life for nefazodone was 8.3 hours, and its metabolite hydroxy(OH)-nefazodone was 14.6 hours. BP-time curves demonstrated an 18-hour period of hypotension. There was a significant correlation between systolic BPand OH-nefazodone (R2 = 0.602). HR remained between 56 and 66 bpm for 30 hours despite hypotension. QT was significantly correlated with nefazodone (R2 = 0.911) and OH-nefazodone (R2 = 0.797), but no significant relationship between QTc and drug concentrations. The case demonstrates that nefazodone may potentially cause cardiac toxicity, which appears to be concentration-dependent. Although QT was concentration-dependent, this would need confirmation with other cases. Bradycardia, hypotension, and drowsiness are the most significant effects and are maximal in the first 12 hours when parent and metabolite concentrations are high.

Adolescent↗

Clinical toxinology--where are we now?

Clinical toxinology encompasses a broad range of medical conditions resulting from envenomation by venomous terrestrial and marine organisms, and also poisoning from ingestion of animal and plant toxins. Toxin-related disease is an important cause of morbidity and mortality worldwide, particularly in the tropical and subtropical continents. Snake bite is the single most important toxin-related disease, causing substantial mortality in many parts of Africa, Asia, and the Americas. The most important snake families are Viperidae and Elapidae, causing a range of clinical effects including local necrosis, neurotoxicity, coagulopathy and hemorrhage, myotoxicity and renal toxicity. These effects vary according to geography and group of snake. Arachnid envenomation results mainly in morbidity, particularly scorpion stings which can cause severe systemic envenomation. Spider bite is far less of a problem, and the majority of medically important cases can be attributed to widow spiders (Latrodectus spp.) and recluse spiders (Loxosceles spp.). Marine-related envenomations are common, but severe effects are less so. Plant and mushroom poisoning occur in most parts of the world, but the types and methods of poisoning vary considerably between continents. Management of toxin-related disease is often difficult, and in many cases meticulous supportive care is all that is available. The mainstay of treatment is the use of antivenoms for many envenomations and poisoning, although these do not exist for all dangerous organisms. Unfortunately antivenoms are not an economically viable product, so development and manufacture of these agents have been limited. This is now further worsened by a current shortage of antivenom. There is a need for improvement in the preventionand management of toxin-related disease. This will require well-designed studies to define the extent of the problem, initiatives to improve the prevention and management of these conditions, and development of new, and continuation of current, antivenom supplies.

Animals↗

Antivenom treatment in arachnidism.

Envenomation by arachnids causes significant medical illness worldwide. Scorpion sting is the most important arachnid envenomation causing adult morbidity and pediatric mortality. Important groups of spiders include the widow spiders (Latrodectus spp.), the recluse spiders (Loxosceles spp.), and two spiders confined to single countries: the Australian funnel web spider (Atrax and Hadronyche spp.) and the armed spider (Phoneutria spp.) from Brazil. There are four widow spider antivenoms available, including the Australian redback spider antivenom and the American black widow antivenom. Despite good in vitro animal work demonstrating effective neutralization with these antivenoms, and cross-reactivity between many species, there continues to be a reluctance to use them in some countries. They are both associated with a relatively low rate of allergic reactions. Redback antivenom is routinely used by the intramuscular route, which may not be as effective as intravenous use based on clinical experience and animal studies. Antivenoms are available for Loxosceles spp., but there is little evidence to support their effectiveness, particularly against local effects. The Australian funnel web spider causes severe neurotoxic envenomation, and antivenom appears to be effective in reported cases. An antivenom exists for the Brazilian armed spider, but is used in only a minority of cases. Many scorpion antivenoms exist worldwide, but there remains significant controversy regarding their efficacy. Animal and human venom level studies demonstrate neutralization of circulating venom in systemic envenomation. Clinical experience in countries where antivenom has been introduced suggests it has reduced pediatric mortality. However, three controlled trials demonstrated that antivenom was not effective, but these included few severe cases. Until controlled trials of antivenom in systemically envenomated patients are undertaken, antivenom use appears justified in severe envenomation. Although envenomation from arthropods is common, no antivenoms exist for these, excepting Lonomia caterpillars in South America, and Ixodes paralysis ticks in Australia.

Animals↗

Randomized controlled trial of topical aspirin in the treatment of bee and wasp stings.

BACKGROUND: The New South Wales Poisons Information Centre (NSW PIC) has been recommending the use of topical aspirin paste for bee and wasp stings since the early 1980s. Anecdotal evidence from calls suggested it was effective in reducing the swelling and duration of pain, but a literature search found no evidence to support this. OBJECTIVE: The objective of this study was to assess the effectiveness of advice given by a PIC to apply topical aspirin for the treatment of bee and wasp stings. METHODS: Patients were recruited from callers to the NSW PIC who reported a bee or wasp sting. They were randomly assigned, using a 2:1 ratio, to two different treatment advices: to apply an ice pack (control group), or to apply an ice pack and topical aspirin paste (treatment group). Initial follow-up was within 24-48 hours. Primary outcome was the presence of swelling at 12 hr. Secondary outcomes included the presence of pain at 12 hr, the presence of itchiness, and duration of redness. RESULTS: There were 37 patients who received treatment advice and 19 in the control group. Of the 37 patients advised to apply aspirin, 21 (57%) had no swelling at 12 hr compared with 14 of the 19 (74%) patients with ice alone (difference -17%; 95% CI: -47-12%; p = 0.26). Eighty-one percent (30/37) of patients advised to apply aspirin had no pain at 12 hr compared with (18/19) 95% of the others (-14%; 95% CI: -39-14%; p = 0.34). The median duration of redness was 6 hr [interquartile range (IQR): 2-48 hr] in those advised to apply aspirin paste compared with 2 hr (IQR: 0-10 hr) in those that only applied ice (p = 0.04). CONCLUSIONS: Topical aspirin paste was not effective in reducing the duration of swelling or pain in bee and wasp stings, and significantly increased the duration of redness. Symptoms rapidly subsided with ice alone as treatment.

Administration, Topical↗

Effects of envenoming by comb-footed spiders of the genera Steatoda and Achaearanea (family Theridiidae: Araneae) in Australia.

BACKGROUND: The family Theridiidae (comb-footed spiders) contains the well-known and medically important widow spider group (Latrodectus spp.). Little is known about the effects of envenoming by other common members of this family. OBJECTIVE: The objective of this study was to determine the clinical effects of bites by common theridiid spiders of the genera Steatoda and Achaearanea. METHODS: This was a prospective cohort study of calls to Australian poison information centers and presentations to emergency departments. Twenty-eight persons with a definite bite by a spider of the family Theridiidae, excluding Latrodectus spp., were included where the spider was immediately collected and expertly identified from February 1999 to April 2002. RESULTS: There were 23 bites by Steatoda spp. and five bites by Achaearanea spp. Steatoda bites occurred across Australia, throughout the year, and the majority during waking hours. Seventy-eight percent of bites occurred indoors and 48% while dressing indoors. Pain was universal and was severe in six (26%). Increasing pain in the first hour occurred in 30%, and the median duration of pain was 6 hr (interquartile range: 1-12 hr). Local or regional diaphoresis did not occur. Systemic effects occurred in 30% and included nausea, headache, lethargy, and malaise. The majority received no treatment: seven patients presented to a hospital (two patients received opiates for analgesia) and 1 patient inadvertently received intravenous redback spider (RBS) antivenom because the spider was initially misidentified as a RBS (Latrodectus). The pain and symptoms responded over 1 hr following antivenom administration. Bites by Achaeranea spp. caused moderate to severe persistent pain, but no systemic effects. CONCLUSIONS: Steatoda spp. bites or "steatodism" may cause prolonged pain and systemic effects similar to Latrodectus bites, but less severe. In severe cases, the clinical effects were almost indistinguishable from Latrodectus, except diaphoresis was absent, and the spiders were often mistaken for Latrodectus. Intravenous RBS antivenom appears to be an effective treatment in isolated severe cases, consistent with in vitro work. Achaearanea bites caused pain similar to Latrodectus bites.

Animals↗

Intentional warfarin overdose.

Warfarin toxicity is common and usually results from dose changes or drug interactions. There are few reported cases of intentional overdose. The management of warfarin overdose is usually complicated by the patient using warfarin therapeutically, often for a mechanical heart valve or pulmonary embolus prophylaxis. Untreated patients have a significant bleeding risk, but treatment carries a significant risk of complete reversal of anticoagulation and consequent risk of thrombosis. The objective of this study was to describe warfarin overdoses and complications of treatment and develop a safe approach to management. Three patients are described. Two patients received a single 10-mg dose of vitamin K. Both required anticoagulation, and in one, warfarin resistance persisted for 2 weeks. In a third patient serial INR, factor levels and warfarin concentrations were measured, and incremental doses of vitamin K (up to 7.5 mg) were given based on INR. This patient did not require anticoagulation, and regular warfarin therapy was recommenced after 4 days. Patients intentionally overdosing on warfarin can be classified into three groups based on preexisting indications for warfarin: nontherapeutic, moderate risk, and major risk for thromboembolic complications. All patients should have regular INR measurements (6-hourly) to catch rapid rises. Patients not on warfarin therapeutically can be given 10 mg of vitamin K1 and repeat INRs as an outpatient. Titrating intravenous vitamin K with doses of 0.5 to 2.0 mg when INR > 5 is appropriate to reduce INR without causing warfarin resistance. The high-risk group must be kept anticoagulated, and warfarin resistance avoided.

Adult↗