Intravenous lipid emulsion as an antidote in clinical toxicology: a systematic review.

OBJECTIVE: Intravenous lipid emulsions (ILE) were developed many decades ago to supply nutritional requirements to patients unable to obtain adequate enteral nutrition. The utility of ILE was extended to therapeutics, facilitating the delivery of drugs. More recently, the potential for ILE to act as an antidote for inversion of drug toxicity has been recognized. This review aims to summarize the literature on ILE therapy as an antidote. Suggested mechanisms of action, safety profile, and recommendations on the administration of ILE in cases of drug intoxication are highlighted. MATERIALS AND METHODS: A complete literature survey was performed using the PubMed database search to collect available information regarding mechanisms of ILE action as an antidote, ILE administration for drug toxicity, and presentation of adverse events. RESULTS: A total of 102 studies met the selection criteria for inclusion in the review. Mainly used for local anesthetics toxicity, ILE therapy has been expanded in clinical toxicology involving overdose treatment of drugs other than local anesthetics. Partitioning in a lipid phase of fat droplets is a mechanism named the lipid sink phenomenon that has primarily been described to explain this action of ILE and remains the most widely accepted. At the same time, recent research has also revealed several molecular mechanisms that may contribute to ILE efficacy. CONCLUSIONS: ILE therapy comprises a recognized approach in clinical toxicology. Due to the lack of randomized clinical trials, recommendations on administration are based on animal studies and published cases. Thus, the constantly increased knowledge about ILE therapy supports the need for a detailed appraisal.

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Effective radiation doses associated with non-invasive versus invasive assessment of coronary anatomy and physiology.

OBJECTIVES: To compare the effective radiation dose (ERD) needed to obtain information on coronary anatomy and physiology by a non-invasive versus an invasive diagnostic strategy. BACKGROUND: Knowledge of anatomy and physiology is needed for management of patients with coronary artery disease (CAD). There is, however, a growing concern about detrimental long-term effects of radiation associated with diagnostic procedures. METHODS: In a total of 671 patients with suspected CAD, we compared the ERD needed to obtain anatomical and physiological information through a non-invasive strategy or an invasive strategy. The non-invasive strategy consisted of coronary computed tomography angiography (CCTA) and single photon emission computed tomography (SPECT). The invasive strategy included coronary angiography (CA) and fractional flow reserve (FFR) measurement. In 464 patients, the data were acquired in Period 2009 and in 207 the data were acquired in Period 2011 (after each period, the CCTA- and the CA-equipment had been upgraded). RESULTS: For the Period 2009 total ERD of the non-invasive approach was significantly larger compared to the invasive approach (28.45 ± 5.37 mSv versus 15.79 ± 7.95 mSv, respectively; P < 0.0001). For Period 2011, despite the significant decrease in ERD for both groups (P<0.0001 for both), the ERD remained higher for the non-invasive approach compared to the invasive approach (16.67 ± 10.45 mSv vs. 10.36 ± 5.87 mSv, respectively; P < 0.0001). Simulation of various diagnostic scenarios showed cumulative radiation dose is the lowest when a first positive test is followed by an invasive strategy. CONCLUSION: To obtain anatomic and physiologic information in patients with suspected CAD, the combination of CA and FFR is associated with lower ERD than the combination of CCTA and SPECT.