If you are in an appropriate medical setting, being monitored, and under the supervision of a physician qualified to react to any potential adverse effects, that is what I would call a “safe setting.”
Not being in the proper medical setting, even with people you trust, is never “safe.” While serious adverse events during Ketamine administration are rare, it is possible to have very dangerous reactions that may even lead to death, without the proper medical personnel and equipment in place.
A “K-holes worth” is not a precise definition. “K-holes” do not have a formal definition. It’s a general term to describe a Ketamine experience that is uncomfortable, frightening, or dangerous.
For instance, one may consider having been in a “K-hole” when their Ketamine session involved intense anxiety, terror, or hallucinations.
As for what a “K-hole's worth of Ketamine” is, it varies by individual. The method of intake (infusion, intramuscular, oral, nasal), dosage, time period (i.e. an hour of steady release, etc), patient's weight, proficiency of the patient's detoxification pathway performance (liver function for example), medications the patient is on, and other factors all affect the qualities of the Ketamine experience.
In short: you wouldn't know if you were going to have a K-hole experience unless you personally received Ketamine under conditions that specified all of the factors above.
Ketamine infusions, for example, generally begin with a baseline dosage based on the patient's weight. Dosage and other factors may be adjusted depending on whether the treatment session was safe and effective. The frequency will need to be a variable determined by your physician.
Please note that the recreational use of Ketamine is never safe. Any number of things can happen; all the way from addiction to death.