Influence of a strict glucose protocol on serum potassium and glucose concentrations and their association with mortality in intensive care patients

INTRODUCTION: Tight glucose control therapy (TGC) has been implemented to control hyperglycemia in ICU patients. TGC may also influence serum potassium concentrations. We therefore investigated the influence of TGC on both serum glucose and serum potassium concentrations and associated mortality. METHOD: We performed a retrospective analysis including all patients admitted to the ICU of a tertiary hospital for 24 hours or more and with at least three serum glucose and serum potassium concentrations between 1999-2001 (conventional period), 2002-2006 (implementation period) or 2007-2009 (TGC period). Segmented regression analysis was used to estimate changes in outcomes that occurred after the intervention controlling for pre-intervention trends. Means and standard deviations (SDs) of serum glucose and serum potassium concentrations, and rate of severe hypoglycemia (≤ 2.2 mmol/L) and hypokalemia (≤ 3 mmol/L), were compared between the TGC and conventional period. RESULTS: Although mean serum glucose concentrations dropped 2.1 mmol/L (95% CI =-1.8 to -2.3 mmol/L, p<0.002), mean serum potassium concentrations did not change (absolute increase 0.02 mmol/L; 95% CI = -0.06 to 0.09 mmol/L, p=0.64). The rate of severe hypoglycemia increased with 5.9% (95% CI=-3.0 to -8.9, p<0.002), but the rate of hypokalemia remained equal (absolute reduction 4.8%; 95% CI = -11.1% to 1.5%, p=0.13). The SD of serum glucose concentrations within a patient did not change, while the SD of serum potassium concentrations even decreased 0.04 mmol/L (95% CI = -0.01 to -0.07, p = 0.01). ICU mortality decreased but this decrease was not significant (absolute difference -3.63%; 95% CI = -9.33 to 2.09, p = 0.20). Mean serum glucose concentrations, mean serum potassium concentrations and SDs of both serum glucose and serum potassium concentrations were all independently associated with ICU mortality. Highest mortality rates were seen at both the lowest and highest mean values (U/J-shaped association) and mortality rates increased with increasing variability (SDs) for both serum glucose and serum potassium concentrations. CONCLUSION: Our study shows that a TGC was not associated with an increased risk of serum potassium related events. Low and high mean values and high variability of both serum glucose and serum potassium concentrations are predictors for high ICU mortality

Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs:the role of the aromatic ring

OBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can explain symptoms of hypersensitivity. METHODS: Between January 1985 and January 2007, all adverse drug reactions (ADRs) reported to the Netherlands Pharmacovigilance Centre Lareb related to AEDs as suspected drugs were included in this study. ADRs were analysed using a case/non-case design. Cases were defined as those patients with ADRs involving symptoms of hypersensitivity. Non-cases were patients with all other ADR reports. Symptoms of hypersensitivity were classified according to the Gell and Coombs classification (type I-IV) and the organ involved (e.g. cutaneous, hepatic). AEDs were classified as aromatic anticonvulsant if their chemical structure contained at least one aromatic ring. All other AEDs were classified as non-aromatic. We assessed the strength of the association between aromatic AEDs versus non-aromatic AEDs and reported hypersensitivity reactions with logistic regression analysis and expressed these as reporting odds ratios (RORs). RESULTS: In total, 303 cases of hypersensitivity associated with the use of AEDs were reported. Aromatic AEDs were suspected in 64.4% of these reports versus 41.3% (574/1389) of the non-hypersensitivity reports. A significant ROR of 2.15 (95% CI 1.63, 2.82) was found for aromatic AEDs and all hypersensitivity reactions. Aromatic AEDs were significantly associated with immunoglobin E-mediated type I hypersensitivity reactions (ROR 2.15; 95% CI 1.23, 3.78) and T-cell-mediated type IV reactions (ROR 6.06; 95% CI 3.41, 10.75). Type II and III reactions did not show an association. Cutaneous symptoms represented 39.9% of the hypersensitivity-related ADRs. Aromatic AEDs were significantly associated with cutaneous hypersensitivity reactions (ROR 5.81; 95% CI 3.38, 9.99). CONCLUSION: This study confirms that the presence of an aromatic ring as a common feature in chemical structures of AEDs partly explains apparent 'idiosyncratic' hypersensitivity reactions. Symptoms of hypersensitivity were reported twice as frequently with aromatic AEDs than with non-aromatic AEDs. Strong associations for aromatic AEDs versus non-aromatic AEDs were found for T-cell-mediated (type IV) reactions, as well as for cutaneous reactions

Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs: the role of the aromatic ring.

Item does not contain fulltextOBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can explain symptoms of hypersensitivity. METHODS: Between January 1985 and January 2007, all adverse drug reactions (ADRs) reported to the Netherlands Pharmacovigilance Centre Lareb related to AEDs as suspected drugs were included in this study. ADRs were analysed using a case/non-case design. Cases were defined as those patients with ADRs involving symptoms of hypersensitivity. Non-cases were patients with all other ADR reports. Symptoms of hypersensitivity were classified according to the Gell and Coombs classification (type I-IV) and the organ involved (e.g. cutaneous, hepatic). AEDs were classified as aromatic anticonvulsant if their chemical structure contained at least one aromatic ring. All other AEDs were classified as non-aromatic. We assessed the strength of the association between aromatic AEDs versus non-aromatic AEDs and reported hypersensitivity reactions with logistic regression analysis and expressed these as reporting odds ratios (RORs). RESULTS: In total, 303 cases of hypersensitivity associated with the use of AEDs were reported. Aromatic AEDs were suspected in 64.4% of these reports versus 41.3% (574/1389) of the non-hypersensitivity reports. A significant ROR of 2.15 (95% CI 1.63, 2.82) was found for aromatic AEDs and all hypersensitivity reactions. Aromatic AEDs were significantly associated with immunoglobin E-mediated type I hypersensitivity reactions (ROR 2.15; 95% CI 1.23, 3.78) and T-cell-mediated type IV reactions (ROR 6.06; 95% CI 3.41, 10.75). Type II and III reactions did not show an association. Cutaneous symptoms represented 39.9% of the hypersensitivity-related ADRs. Aromatic AEDs were significantly associated with cutaneous hypersensitivity reactions (ROR 5.81; 95% CI 3.38, 9.99). CONCLUSION: This study confirms that the presence of an aromatic ring as a common feature in chemical structures of AEDs partly explains apparent 'idiosyncratic' hypersensitivity reactions. Symptoms of hypersensitivity were reported twice as frequently with aromatic AEDs than with non-aromatic AEDs. Strong associations for aromatic AEDs versus non-aromatic AEDs were found for T-cell-mediated (type IV) reactions, as well as for cutaneous reactions